The DOI matches its Crossref record; 208 of the 208 references it cites were found in a registry or an index; 73 of the 94 sources its claims cite were checked for support.
Type 1 interferon perturbates clonal competition by reshaping human blood development
Open accessAbstract
Abstract Inflammation perturbs evolutionary dynamics of hematopoietic stem cell (HSC) clones in clonal hematopoiesis and myeloid neoplasms. We studied HSCs, progenitors and immune cells from patients with myeloproliferative neoplasm (MPN) at baseline and following interferon-⍺ (IFN⍺) treatment, the only MPN therapy to deplete clonal stem cells. We focused on essential thrombocythemia, an informative model of early-phase neoplastic hematopoiesis. We integrated somatic genotyping, transcriptomes, immunophenotyping, and chromatin accessibility across single cells. IFN⍺ simultaneously activated HSCs into two polarized states, a lymphoid progenitor expansion associated with an anti-inflammatory state and an IFN⍺-specific inflammatory granulocytic progenitor (IGP) state derived directly from HSCs. The augmented lymphoid differentiation balanced the typical MPN-induced myeloid bias, associated with normalized blood counts. Clonal fitness upon IFN⍺ exposure was due to resistance of clonal stem cells to differentiate into IGPs. These results support a paradigm wherein inflammation perturbs clonal dynamics by HSC induction into the precipitous IGP differentiation program. One-Sentence Summary Inflammation accelerates clonal evolution by driving stem cell differentiation into an alternate interferon-⍺-induced progenitor state.
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TL;DR
In serial bone marrow from patients with CALR-mutated essential thrombocythemia treated with pegylated IFN-alpha, single-cell multi-omics linked somatic genotype, transcriptome, immunophenotype, and chromatin accessibility in the same CD34+ cells. IFN-alpha simultaneously induced a novel inflammatory granulocytic progenitor state and lymphoid expansion while downregulating TNF-alpha/TGF-beta programs, with mutated cells showing constrained lymphoid expansion and greater myeloid proliferation.
Key findings
- GoT-IM captured CALR genotype for 81.5% of CD34+ HSPCs (n = 40,668) and integrated 49,891 cells from 16 samples; it identified a novel IFN-alpha-induced inflammatory granulocytic progenitor (IGP) state marked by AP-1, KLF, NR4A, RFX2/3, CEBPB/D, and IRF1, with TNF-alpha via NF-kB upregulation (Adj. P = 3.5 × 10−8) and MYC target downregulation (Adj. P = 6.8 × 10−6) versus IMPs.
- IFN-alpha expanded lymphoid progenitors, especially large and small Pre-B cells, and reduced megakaryocytic-erythroid progenitors; Pro-B cells in G2/M/S increased almost 2-fold on average, and MEP/MkP frequencies modeled platelet counts (P = 0.0071, F-test).
- IFN-alpha broadly downregulated TNF-alpha signaling via NF-kB and TGF-beta signaling across progenitor subsets, including downregulation of NFKB1, VEGFA, MAP3K8, IL1B, THBS1, and SERPINE1; HSCs also downregulated CXCR4, with high-CXCR4 HSCs less likely to be in cell cycle (P < 2.2 × 10−22, Fisher exact test).
- In CALR-mutated versus wildtype cells, lymphoid expansion occurred in both but was constrained in mutated cells by relative myeloid expansion; IFNa boosted proliferation more in mutated HSCs and myeloid progenitors, and GoT-ATAC identified PU.1 as a master regulator, with enhanced CEBPA and GATA1 activities in mutated cells.
Methods
- Cryopreserved bone marrow or peripheral blood mononuclear cells from patients with CALR-mutated essential thrombocythemia treated with weekly pegylated IFN-alfa2a in clinical trials MPN-RC-111 and MPN-RC-112 (n = 4 baseline and 7 treated samples from 5 individuals; additional baseline samples from prior work); CD34+ cells were FACS-isolated.
- GoT-IM combined 10x scRNA-seq, CITE-seq immunophenotyping, cell hashing for treatment time point, and targeted CALR genotyping; GoT-ATAC adapted 10x Multiome to capture snRNA-seq, snATAC-seq, and somatic genotype (n = 24,862 total cells; 12% genotyped, n = 2,873 cells; n = 4 baseline, 3 treated samples).
- Analyses included Seurat canonical correlation integration, Ironthrone-GoT mutation calling, linear mixed models, pre-ranked GSEA against MSigDB Hallmark sets, chromVAR motif enrichment, gene-peak cis-association, multiplexed immunofluorescence, and retrospective flow cytometry (n = 47 no IFNa, n = 9 IFNa).
Limitations
- The paper states that serial bone marrow specimens are exceedingly rare, the cohort is small, and cryopreserved mononuclear cells precluded assessment of neutrophils; GoT-ATAC genotyping efficiency was significantly lower than GoT-IM due to the limited nuclear transcript pool.
- The paper notes that IGPs constitute <1% of progenitors, making functional and genetic lineage studies challenging, and that in vitro IFN-alpha effects on HSCs differ from in vivo effects; it also raises the possibility that the IGP population may not be present in mice.
- The text makes evident additional constraints: the multiplexed immunofluorescence validation used a non-paired cohort with only a trending increase in proliferation (P = 0.063, Wilcoxon rank sum), and the double-mutant CALR clone analysis rests on a single index patient (IFN04).
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Claims the paper makes
85 Own result · 31 Own interpretation · 25 Couldn’t confirm · 17 Own method · 11 Partly supported · 8 No full text of the sources · 2 No basis given · 1 Sources not found · 1 Not checked yet · accuracy not yet measured
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“Interestingly, while IFNa alters mouse HSC marker Sca-1 2 (rendering difficult the quantification of progenitor cell frequency changes by flow cytometric assessment in mice), IFNa did not alter CD90 expression after treatment in the HSPCs ( Fig. 2e, Supplementary Fig. 3c ).”
What the sources say
- Could not verifycites [2] Jaiswal, S. et al. Age-related clonal hematopoiesis associated with adverse outcomes. N. Engl. J. Med. 371, 2488–2498 (2014). sourceExperimental — accuracy not yet measured
The Results section discusses blood-cell indexes and somatic mutations, not IFNα treatment or CD90 expression in HSPCs. Searches for the quoted claim and for IFNα, CD90, and Sca-1 found no passage in our copy that addresses the claim; the citing sentence instead points to its own figures. (LLM, conf=0.75)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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- Could not verify
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“These findings contrasted with the more subtle transcriptional impact of CALR -mutations, since mutated and wildtype cells are co-mingled throughout differentiation 20,39 .”
What the sources say
- Could not verifycites [20] Pourcelot, E. et al. Cytokine profiles in polycythemia vera and essential thrombocythemia patients: clinical implications. Exp. Hematol. 42, 360–368 (2014). sourceExperimental — accuracy not yet measured
The Discussion and “Impact of JAK2 status” sections address JAK2 V617F and cytokine profiles, not CALR mutations. Searches for CALR, transcriptional effects, and co-mingling of mutant and wild-type cells during differentiation found no passage addressing the claim. Page numbers were not available in our copy. (LLM, conf=0.76)
- Could not verifycites [39] Van Egeren, D. et al. Reconstructing the lineage histories and differentiation trajectories of individual cancer cells in myeloproliferative neoplasms. Cell Stem Cell 28, 514–523 (2021). sourceExperimental — accuracy not yet measured
The Results section (‘JAK2-Mutant HSPCs Exhibit Fate Bias’; page unavailable) reports similar expression profiles and intermixing for JAK2-V617F and wild-type cells, not CALR-mutant cells. Searches for CALR and calreticulin found no passage in our copy addressing CALR mutations’ transcriptional impact or their distribution through differentiation. (LLM, conf=0.76)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Could not verify
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“Consistent with previous reports in mice 43 , the proportions of HSCs expressing G2/M/S-phase genes were enhanced upon IFNa treatment ( Fig. 2h,i) .”
What the sources say
- Could not verifycites [43] Tirosh, I. et al. Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq. Science 352, 189–196 (2016). sourceExperimental — accuracy not yet measured
The section on malignant-cell cell cycles (page unavailable) describes G1/S and G2/M signatures in melanoma cells, not HSCs. Searches for IFNa treatment, hematopoietic stem cells, and mouse HSC proliferation found no passage addressing the cited prior report. (LLM, conf=0.76)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Could not verify
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“Interestingly, MYC targets were also upregulated ( Fig. 2k, Supplementary Table 6 ), thus corroborating a previous report demonstrating that IFNa upregulates MYC protein, which was thus postulated to regulate the cell cycle entry of HSCs in mice 52 .”
What the sources say
- Could not verifycites [52] Jakobsen, N. A. et al. Selective advantage of mutant stem cells in human clonal hematopoiesis is associated with attenuated response to inflammation and aging. Cell Stem Cell 31, 1127–1144 (2024). sourceExperimental — accuracy not yet measured
The Results sections on TET2-mutant progenitors and inflammatory responses report changes in other gene signatures, but do not identify upregulated MYC targets. Searches for MYC and for IFN-α-induced MYC protein in mouse HSCs found no passage addressing either point. The cited paper therefore does not verify the MYC claim in our copy. (LLM, conf=0.73)
plain- Asserted: passes — The authors put it forward as true.
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The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“We and others have shown that MPN megakaryocytes indeed exhibit higher expression of TGFB1 20,50,51 , and thus downregulation of TGFB1 by IFNa may be a key mechanism of improvement in fibrosis frequently observed in patients treated with IFNa.”
What the sources say
- Could not verifycites [20] Pourcelot, E. et al. Cytokine profiles in polycythemia vera and essential thrombocythemia patients: clinical implications. Exp. Hematol. 42, 360–368 (2014). sourceExperimental — accuracy not yet measured
The Methods section lists the 13 plasma cytokines measured, but TGFB1 is not among them. The Discussion links megakaryocytes to PDGF-BB synthesis, not to higher TGFB1 expression. Searches for TGFB1 and transforming growth factor beta found no passage addressing the attributed claim; page numbers were unavailable in our copy. (LLM, conf=0.76)
- Partly supportedcites [50] Badalucco, S. et al. Involvement of TGFβ1 in autocrine regulation of proplatelet formation in healthy subjects and patients with primary myelofibrosis. Haematologica 98, 514–517 (2013). sourceExperimental — accuracy not yet measured
Figure 2 and the results (p. 516) show that megakaryocytes from patients with primary myelofibrosis released more total and bioactive TGFβ1 than healthy controls. The paper does not establish higher TGFB1 gene expression or show that the finding extends to MPN megakaryocytes generally. The IFNa proposal follows the cited clause and is not treated as attributed to this source. (LLM, conf=0.84)
- Could not verifycites [51] Kaufmann, K. B. et al. A latent subset of human hematopoietic stem cells resists regenerative stress to preserve stemness. Nat. Immunol. 22, 723–734 (2021). sourceExperimental — accuracy not yet measured
The Extended Data Fig. 6 description (p. 5) mentions megakaryocytic cells only as an output of stem-cell differentiation assays; it does not address MPN megakaryocytes or TGFB1 expression. Searches for “MPN megakaryocytes TGFB1,” “transforming growth factor beta 1,” and “TGFB1” found no passage supporting the attributed comparison. (LLM, conf=0.75)
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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- Could not verify
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“We also observed a downregulation of TGFB1 ( Supplementary Fig. 4b ), that encodes the pro-fibrotic cytokine TGFb established as one of the main inducers of myelofibrosis in patients with fibrotic-phase of MPN 50,51 .”
What the sources say
- Partly supportedcites [50] Badalucco, S. et al. Involvement of TGFβ1 in autocrine regulation of proplatelet formation in healthy subjects and patients with primary myelofibrosis. Haematologica 98, 514–517 (2013). sourceExperimental — accuracy not yet measured
The citation is attached to the background claim about TGFβ and myelofibrosis, not to the citing authors’ observation of TGFB1 downregulation after IFNα treatment. The source describes TGFβ1 as having a crucial role in primary myelofibrosis pathogenesis, but its discussion of TGFβ1 promoting bone-marrow fibrosis is framed as a hypothesis, not an established finding that it is one of the main inducers. (LLM, conf=0.84)
- Could not verifycites [51] Kaufmann, K. B. et al. A latent subset of human hematopoietic stem cells resists regenerative stress to preserve stemness. Nat. Immunol. 22, 723–734 (2021). sourceExperimental — accuracy not yet measured
The cited paper’s PAK4-inhibition section (pp. 20–21) discusses hematopoietic stem-cell responses to a PAK4 inhibitor, not IFNα treatment. Searches for TGFB1 downregulation and IFNα treatment found no passage addressing the claim. In the citing sentence, references 50 and 51 appear attached to TGFβ’s role in myelofibrosis, while the downregulation is presented as the citing authors’ own observation. (LLM, conf=0.76)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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- Partly supported
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“As IFNa has been shown to induce HSC and progenitors into cell cycle entry 43 , we posited that differential induction of progenitor subtypes into proliferation may underlie the shifts in differentiation.”
What the sources say
- Could not verifycites [43] Tirosh, I. et al. Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq. Science 352, 189–196 (2016). sourceExperimental — accuracy not yet measured
The section on cell-cycle heterogeneity describes cycling malignant melanoma cells, not hematopoietic stem cells or progenitors. Searches for IFN-alpha, HSCs, and hematopoietic progenitor cell-cycle entry found no passage in our copy addressing whether IFN-alpha induces those cells to enter the cell cycle; no page numbers were supplied. (LLM, conf=0.76)
boosteddirect- Asserted: passes — The authors put it forward as true.
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- Could not verify
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“Upregulation of CEBPB and CEBPD ( Fig. 1e left, Supplementary Fig. 2d, Supplementary Table 3 ), implicated in emergency granulopoiesis 30 and granulopoiesis under cellular stress 31 respectively, suggested a differentiation state into the granulocytic lineage.”
What the sources say
- Could not verifycites [30] Stoeckius, M. et al. Simultaneous epitope and transcriptome measurement in single cells. Nat. Methods 14, 865–868 (2017). sourceExperimental — accuracy not yet measured
The passages on immune-cell characterization discuss CITE-seq markers and NK-cell subsets, not CEBPB or CEBPD. Searches for those genes, emergency granulopoiesis, and granulocytic-lineage differentiation found no passage in our copy addressing the claim. (LLM, conf=0.76)
- Could not verifycites [31] Butler, A., Hoffman, P., Smibert, P., Papalexi, E. & Satija, R. Integrating single-cell transcriptomic data across different conditions, technologies, and species. Nat. Biotechnol. 36, 411–420 (2018). sourceExperimental — accuracy not yet measured
The Results section discusses hematopoietic progenitor lineages, but does not link CEBPB or CEBPD upregulation to granulocytic differentiation. Searches for those genes, emergency granulopoiesis, and granulopoiesis under cellular stress found no passage addressing the claim; page numbers were unavailable in our copy. (LLM, conf=0.72)
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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- Could not verify
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In the MkPs, we identified a downregulation of CD9 and VWF , closely associated with MkP differentiation 46-49 , upon IFNa treatment ( Supplementary Fig. 4b ) which is consistent with the decrease in the proportion of MkP observed after IFNa treatment.”
What the sources say
- Partly supportedcites [46] Nam, A. S. et al. Single-cell multi-omics of human clonal hematopoiesis reveals that DNMT3A R882 mutations perturb early progenitor states through selective hypomethylation. Nat. Genet. 54, 1514–1526 (2022). sourceExperimental — accuracy not yet measured
The Results section on the DNMT3A-mutated bone marrow sample says CD9 expression has been linked with megakaryocytic differentiation priming and examines it along that differentiation trajectory. The passages found do not establish the same association for VWF; they also do not address IFNa treatment, which the citing sentence presents as its own finding. No page number was provided for these passages. (LLM, conf=0.86)
- Could not verifycites [47] Nie, Y., Han, Y. C. & Zou, Y. R. CXCR4 is required for the quiescence of primitive hematopoietic cells. J. Exp. Med. 205, 777–783 (2008). sourceExperimental — accuracy not yet measured
The Results and Discussion passages address CXCR4-dependent hematopoietic stem-cell quiescence and differentiation, not MkP differentiation. Searches for CD9, VWF, megakaryocyte progenitors, and related terms found no passage connecting either marker to MkP differentiation. Page numbers were not available in our copy. (LLM, conf=0.76)
- Not checked — no full text of the sourcecites [48] Ciurea, S. O. et al. Pivotal contributions of megakaryocytes to the biology of idiopathic myelofibrosis. Blood 110, 986–993 (2007). source
- Could not verifycites [49] Chagraoui, H. et al. Prominent role of TGF-beta 1 in thrombopoietin-induced myelofibrosis in mice. Blood 100, 3495–3503 (2002). sourceExperimental — accuracy not yet measured
The Marrow cell preparation and infection section describes progenitor-cell enrichment, and the Pathological changes in tissues section describes megakaryocyte proliferation, but neither links CD9 or VWF to MkP differentiation. Searches for CD9, VWF, and megakaryocytic differentiation found no passage addressing that link; page numbers were unavailable in our copy. (LLM, conf=0.76)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“We and others have shown that MPN megakaryocytes indeed exhibit higher expression of TGFB1 20,50,51 , and thus downregulation of TGFB1 by IFNa may be a key mechanism of improvement in fibrosis frequently observed in patients treated with IFNa.”
What the sources say
- Could not verifycites [20] Pourcelot, E. et al. Cytokine profiles in polycythemia vera and essential thrombocythemia patients: clinical implications. Exp. Hematol. 42, 360–368 (2014). sourceExperimental — accuracy not yet measured
The citation is attached to the statement that MPN megakaryocytes have higher TGFB1 expression, but the indexed paper does not address TGFB1 expression. Its cytokine-assay methods list IFN-gamma, not IFN-alpha or TGFB1; the treatment discussion concerns JAK inhibitors, not IFN-alpha or fibrosis improvement. Searches for TGFB1 in megakaryocytes and for IFN-alpha–related fibrosis found no supporting passage. The proposed mechanism after the citation is the citing authors’ inference. (LLM, conf=0.76)
- Supportedcites [50] Badalucco, S. et al. Involvement of TGFβ1 in autocrine regulation of proplatelet formation in healthy subjects and patients with primary myelofibrosis. Haematologica 98, 514–517 (2013). source
The citation is attached to the statement that MPN megakaryocytes have higher TGFB1 levels. The Results (p. 516) report increased total and bioactive TGFβ1 released by megakaryocytes from patients with primary myelofibrosis compared with controls. The proposed effect of IFNα on fibrosis is the citing authors’ subsequent inference, not a finding attributed to this source. (LLM, conf=0.91)
- Could not verifycites [51] Kaufmann, K. B. et al. A latent subset of human hematopoietic stem cells resists regenerative stress to preserve stemness. Nat. Immunol. 22, 723–734 (2021). sourceExperimental — accuracy not yet measured
The citation in the printed sentence follows the claim that MPN megakaryocytes have higher TGFB1 expression; the IFNa–fibrosis mechanism is the citing authors’ subsequent inference. Our copy’s PAK4-inhibition section (pp. 20–21) discusses hematopoietic stem-cell cycling, not either TGFB1 expression in MPN megakaryocytes or IFNa-associated fibrosis improvement. Searches for TGFB1, MPN megakaryocytes, and IFNa found no passage addressing those points. (LLM, conf=0.72)
hedgedconditional- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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- Could not verify
- Probably not a substantial claim. 38
- It may state two separate claims as one. 43
- The quote only partly states this claim. 2
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The isolated effects of individual inflammatory cytokines, including type 1 interferons (IFNa/b) 1-3 , type 2 IFN (IFNg) 4-6 , TNFa 7,8 , and IL-1 9-11 , have been well-documented in mouse hematopoietic development.”
What the sources say
- Could not verifycites [1] Jaiswal, S. et al. Clonal hematopoiesis and risk of atherosclerotic cardiovascular disease. N. Engl. J. Med. 377, 111–121 (2017). sourceExperimental — accuracy not yet measured
The Results section reports increased IL-1β and other inflammatory molecules in Tet2-deficient mouse macrophages, while the Discussion concerns inflammation and atherosclerosis. Neither addresses the isolated effects of interferons, TNFα, or IL-1 on mouse hematopoietic development. Searches for those cytokines and hematopoietic development found no supporting passage in our copy; page numbers were unavailable. (LLM, conf=0.76)
- Could not verifycites [2] Jaiswal, S. et al. Age-related clonal hematopoiesis associated with adverse outcomes. N. Engl. J. Med. 371, 2488–2498 (2014). sourceExperimental — accuracy not yet measured
The Discussion describes murine models of DNMT3A or TET2 loss of function, not the effects of individual inflammatory cytokines on mouse hematopoietic development. Searches for interferons, TNF, IL-1, and cytokine effects found no passage addressing the claim in our copy; page numbers were not provided. (LLM, conf=0.76)
- Could not verifycites [3] Busque, L. et al. Recurrent somatic TET2 mutations in normal elderly individuals with clonal hematopoiesis. Nat. Genet. 44, 1179–1181 (2012). sourceExperimental — accuracy not yet measured
The paper’s Abstract discusses TET2 mutations in elderly people with clonal hematopoiesis and cites murine findings about Tet2 loss and stem-cell behavior. Searches for inflammatory cytokines, interferons, TNFα, and IL-1 found no passage addressing their isolated effects in mouse hematopoietic development. (LLM, conf=0.76)
- Not checked — no full text of the sourcecites [4] Avagyan, S. et al. Resistance to inflammation underlies enhanced fitness in clonal hematopoiesis. Science 374, 768–772 (2021). source
- Could not verifycites [5] Heyde, A. et al. Increased stem cell proliferation in atherosclerosis accelerates clonal hematopoiesis. Cell 184, 1348–1361 (2021). sourceExperimental — accuracy not yet measured
The Introduction says that increased cytokine levels may drive hematopoietic activity, but it does not identify TNFα or document its isolated effects in mouse hematopoiesis. Searches for TNF and tumor necrosis factor found no passage addressing the TNFα-specific claim. (LLM, conf=0.72)
- Could not verifycites [6] Meisel, M. et al. Microbial signals drive pre-leukaemic myeloproliferation in a Tet2-deficient host. Nature 557, 580–584 (2018). sourceExperimental — accuracy not yet measured
The paper discusses IL-6-driven myelopoiesis in Tet2-deficient mice (Abstract and Extended Data Fig. 10; page not specified). Searches for IL-1, interferons and TNF did not find passages documenting the isolated effects of the cytokines named in the citing sentence. (LLM, conf=0.77)
- Supportedcites [7] Cai, Z. et al. Inhibition of inflammatory signaling in Tet2 mutant preleukemic cells mitigates stress-induced abnormalities and clonal hematopoiesis. Cell Stem Cell 23, 833–849 (2018). source
The Discussion states that IFNα, IFNγ, IL-1α, IL-1β, and TNFα can directly activate hematopoietic stem cells, citing earlier studies. This supports the citing sentence’s broad background point that individual inflammatory cytokines have documented effects on mouse hematopoiesis. (LLM, conf=0.86)
- Partly supportedcites [8] Trowbridge, J. J. & Starczynowski, D. T. Innate immune pathways and inflammation in hematopoietic aging, clonal hematopoiesis, and MDS. J. Exp. Med. 218, e20201544 (2021). sourceExperimental — accuracy not yet measured
The “Inflamm-aging and CHIP” section (page unavailable) reports effects of type I IFN signaling on HSCs in young mice and states that IFN-γ drives expansion of Dnmt3a-knockout HSCs. The “Preleukemia and MDS” section reports that targeting TNF restores HSC function in a mouse model. The copy mentions IL-1β in inflammatory contexts but does not document an isolated effect of IL-1 on mouse hematopoietic development; its examples also focus on HSC function, aging, and premalignancy rather than hematopoietic development generally. (LLM, conf=0.84)
- Not checked — no full text of the sourcecites [9] Essers, M. A. et al. IFNalpha activates dormant haematopoietic stem cells in vivo. Nature 458, 904–908 (2009). source
- Supportedcites [10] Pietras, E. M. et al. Re-entry into quiescence protects hematopoietic stem cells from the killing effect of chronic exposure to type I interferonsIFN-1 effects on HSC function. J. Exp. Med. 211, 245–262 (2014). source
This citation is attached to type I interferons, not to the other cytokines listed. In the Results section (“Chronic IFN-1 exposure causes BM aplasia”), the paper reports effects of acute and chronic type I interferon exposure on mouse bone marrow and blood-cell populations. (LLM, conf=0.94)
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Could not verify
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“Recent reports, for example, link germline genetic defects in type 1 IFN with exaggerated or severe COVID-19 response associated with neutrophilia 16,17 .”
What the sources say
- Could not verifycites [16] Ferrucci, L. et al. The origins of age-related proinflammatory state. Blood 105, 2294–2299 (2005). sourceExperimental — accuracy not yet measured
The Results and Discussion address age-related inflammatory markers and cardiovascular risk factors, not COVID-19. Searches for type 1 IFN defects, neutrophilia, and viral infection found no passage in our copy supporting the claimed link. (LLM, conf=0.78)
- Not checked — no full text of the sourcecites [17] Elliott, M. J. et al. Randomised double-blind comparison of chimeric monoclonal antibody to tumour necrosis factor alpha (cA2) versus placebo in rheumatoid arthritis. Lancet 344, 1105–1110 (1994). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Could not verify
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“In HSCs, we identified a downregulation of CXCR4 gene expression ( Fig. 2j, Supplementary Table 5) , a key regulator of HSC quiescence 45 , which may thus be involved in cell cycle entry of HSCs.”
What the sources say
- Could not verifycites [45] García-García, I. et al. Pharmacokinetic and pharmacodynamic comparison of two ‘pegylated’ interferon alpha-2 formulations in healthy male volunteers: a randomized, crossover, double-blind study. BMC Pharmacol. 10, 15 (2010). sourceExperimental — accuracy not yet measured
The Discussion (page unavailable) describes interferon-induced pharmacodynamic markers, while Methods > Clinical and laboratory evaluations (page unavailable) describes measurement of 2',5' OAS expression. Searches for CXCR4, HSC quiescence, and hematopoietic stem-cell cell-cycle regulation found no passage in our copy addressing the attributed claim. (LLM, conf=0.77)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
- Could not verify
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“These cytokines display overlapping features, such as inducing cell cycle entry of HSCs and their differentiation, frequently toward the granulo-monocytic lineage 1,4-6,12-15 .”
What the sources say
- Could not verifycites [1] Jaiswal, S. et al. Clonal hematopoiesis and risk of atherosclerotic cardiovascular disease. N. Engl. J. Med. 377, 111–121 (2017). sourceExperimental — accuracy not yet measured
The Results report increased cytokine and chemokine secretion by Tet2-deficient macrophages, while the Discussion considers a possible proliferative advantage of hematopoietic progenitors. Neither passage says that cytokines induce HSC cell-cycle entry or differentiation toward the granulo-monocytic lineage. Searches for those effects found no supporting passage in our copy. (LLM, conf=0.72)
- Not checked — no full text of the sourcecites [4] Avagyan, S. et al. Resistance to inflammation underlies enhanced fitness in clonal hematopoiesis. Science 374, 768–772 (2021). source
- Partly supportedcites [5] Heyde, A. et al. Increased stem cell proliferation in atherosclerosis accelerates clonal hematopoiesis. Cell 184, 1348–1361 (2021). sourceExperimental — accuracy not yet measured
The Introduction (page unavailable) says increased cytokine levels may drive hematopoietic activity, and the Results section on sleep fragmentation describes CSF1-dependent proliferation with increased HSC cycling. The paper also reports increased granulocyte/monocyte progenitor activity in atherosclerosis, but it does not establish that the cytokines induce HSC differentiation frequently toward that lineage. (LLM, conf=0.81)
- Partly supportedcites [6] Meisel, M. et al. Microbial signals drive pre-leukaemic myeloproliferation in a Tet2-deficient host. Nature 557, 580–584 (2018). sourceExperimental — accuracy not yet measured
The paper’s section labeled Abstract reports that IL-6 activates myelopoiesis and that IL-6-dependent granulocyte–macrophage progenitor expansion occurs in Tet2-deficient mice. It does not show that cytokines generally induce HSC cell-cycle entry or directly drive HSC differentiation toward that lineage. (LLM, conf=0.86)
- Not checked — no full text of the sourcecites [12] Rao, T. N. et al. JAK2-V617F and interferon-α induce megakaryocyte-biased stem cells characterized by decreased long-term functionality. Blood 137, 2139–2151 (2021). source
- Partly supportedcites [13] Mosca, M. et al. Inferring the dynamics of mutated hematopoietic stem and progenitor cells induced by IFNα in myeloproliferative neoplasms. Blood 138, 2231–2243 (2021). sourceExperimental — accuracy not yet measured
The Discussion (page not available) says IFNα treatment promotes exit from quiescence and differentiation of mutated HSCs into progenitors, supporting those features for IFNα. It does not establish that differentiation is frequently toward the granulo-monocytic lineage, and its findings concern mutated HSCs in myeloproliferative neoplasms rather than HSCs generally. (LLM, conf=0.86)
- Not checked — no full text of the sourcecites [14] Spivak, J. L. Myeloproliferative neoplasms. N. Engl. J. Med. 377, 895–896 (2017). source
- Not checked — no full text of the sourcecites [15] Franceschi, C. et al. Inflamm-aging. An evolutionary perspective on immunosenescence. Ann. N. Y. Acad. Sci. 908, 244–254 (2000). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Could not verify
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Previously, induction of IFNa in mice have yielded mixed results demonstrating either an upregulation 2 or downregulation 53 of TNFa.”
What the sources say
- Could not verifycites [2] Jaiswal, S. et al. Age-related clonal hematopoiesis associated with adverse outcomes. N. Engl. J. Med. 371, 2488–2498 (2014). sourceExperimental — accuracy not yet measured
The Discussion describes murine models of DNMT3A or TET2 loss of function, not IFNα induction or changes in TNFα. Searches of our copy for IFNα, TNFα, and their spelled-out names found no passage addressing the cited downregulation result. (LLM, conf=0.75)
- Partly supportedcites [53] Rodriguez-Meira, A. et al. Single-cell multi-omics identifies chronic inflammation as a driver of TP53-mutant leukemic evolution. Nat. Genet. 55, 1531–1541 (2023). sourceExperimental — accuracy not yet measured
The Results section (‘Inflammation promotes TP53-associated clonal dominance’; page unavailable) reports downregulated TNFα-associated gene signatures in human TP53-heterozygous cells, alongside increased interferon-response genes. It specifies that these patients had no concurrent interferon treatment. This does not establish that inducing IFNα in mice downregulated TNFα—the part of the sentence to which this citation is attached. (LLM, conf=0.82)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Could not verify
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“Although RFX2/3 are not well characterized in hematopoiesis, other RFX members such as RFX1 and RFX8 have been demonstrated to regulate MHC class II expression 35-37 .”
What the sources say
- Could not verifycites [35] Triana, S. et al. Single-cell proteo-genomic reference maps of the hematopoietic system enable the purification and massive profiling of precisely defined cell states. Nat. Immunol. 22, 1577–1589 (2021). sourceExperimental — accuracy not yet measured
The Results passages on surface markers and data-driven flow cytometry discuss hematopoietic cell states, but do not address RFX1 or RFX8 regulation of MHC class II. Further searches for those factors and for MHC class II found no passage supporting the attributed claim. (LLM, conf=0.76)
- Could not verifycites [36] Hay, S. B., Ferchen, K., Chetal, K., Grimes, H. L. & Salomonis, N. The Human Cell Atlas bone marrow single-cell interactive web portal. Exp. Hematol. 68, 51–61 (2018). sourceExperimental — accuracy not yet measured
The Results passages describe bone marrow cell populations and lineage trajectories, not regulation of MHC class II expression. Searches for RFX1, RFX8, and MHC class II found no passage in our copy addressing the attributed claim. (LLM, conf=0.76)
- Could not verifycites [37] Psaila, B. et al. Single-cell analyses reveal megakaryocyte-biased hematopoiesis in myelofibrosis and identify mutant clone-specific targets. Mol. Cell 78, 477–492 (2020). sourceExperimental — accuracy not yet measured
The Results passages on myelofibrosis progenitors and transcription-factor expression (page numbers unavailable) do not address regulation of MHC class II by RFX1 or RFX8. Searches for those factors and for MHC class II regulation found no passage in our copy that speaks to the claim. (LLM, conf=0.72)
boosteddirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Could not verify
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“NR4A1/2 have been demonstrated to maintain HSC quiescence 32-34 .”
What the sources say
- Could not verifycites [32] Hao, Y. et al. Integrated analysis of multimodal single-cell data. Cell 184, 3573–3587 (2021). sourceExperimental — accuracy not yet measured
The Results section on multimodal heterogeneity within lymphoid populations discusses T-cell and NK-cell states, not HSC quiescence. Searches for NR4A1/NR4A2 and hematopoietic stem-cell quiescence found no passage in our copy addressing the claim; page numbers were not available. (LLM, conf=0.76)
- Could not verifycites [33] Velten, L. et al. Human haematopoietic stem cell lineage commitment is a continuous process. Nat. Cell Biol. 19, 271–281 (2017). sourceExperimental — accuracy not yet measured
The Results section ('Molecular processes underlying HSC commitment'; page not provided) associates the least-primed HSC state with cell-cycle quiescence, but does not say that NR4A1 or NR4A2 maintains it. Searches for 'NR4A1/2' and for those factors with HSC quiescence found no passage addressing their role. (LLM, conf=0.72)
- Could not verifycites [34] Popescu, D. M. et al. Decoding human fetal liver haematopoiesis. Nature 574, 365–371 (2019). sourceExperimental — accuracy not yet measured
The Results section ('HSC/MPP differentiation potential by age'; page unavailable) reports a progressive shift toward quiescence in fetal liver HSC/MPPs, but does not link that shift to NR4A1 or NR4A2. Searches for NR4A1, NR4A1/NR4A2, and maintenance of HSC quiescence found no passage in our copy addressing the claimed role of those genes. (LLM, conf=0.76)
boosteddirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
- Could not verify
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“Interestingly, MYC targets were also upregulated ( Fig. 2k, Supplementary Table 6 ), thus corroborating a previous report demonstrating that IFNa upregulates MYC protein, which was thus postulated to regulate the cell cycle entry of HSCs in mice 52 .”
What the sources say
- Could not verifycites [52] Jakobsen, N. A. et al. Selective advantage of mutant stem cells in human clonal hematopoiesis is associated with attenuated response to inflammation and aging. Cell Stem Cell 31, 1127–1144 (2024). sourceExperimental — accuracy not yet measured
The Results section on inflammatory transcriptional programs reports IFN-α response signatures in human HSC/MPPs, but does not say that IFN-α increases MYC protein or that MYC regulates cell-cycle entry in mouse HSCs. Searches for MYC and for the proposed IFN-α–MYC mechanism found no passage addressing that claim; page numbers were not available in our copy. (LLM, conf=0.75)
boosteddirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Could not verify
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“We also observed a downregulation of TGFB1 ( Supplementary Fig. 4b ), that encodes the pro-fibrotic cytokine TGFb established as one of the main inducers of myelofibrosis in patients with fibrotic-phase of MPN 50,51 .”
What the sources say
- Partly supportedcites [50] Badalucco, S. et al. Involvement of TGFβ1 in autocrine regulation of proplatelet formation in healthy subjects and patients with primary myelofibrosis. Haematologica 98, 514–517 (2013). sourceExperimental — accuracy not yet measured
The Introduction states that TGFβ1 is a major contributor to bone-marrow fibrosis in disorders including myelofibrosis, and identifies primary myelofibrosis as a myeloproliferative neoplasm. It does not specifically address patients in the fibrotic phase of MPN or state that the TGFB1 gene encodes TGFβ. (LLM, conf=0.83)
- Could not verifycites [51] Kaufmann, K. B. et al. A latent subset of human hematopoietic stem cells resists regenerative stress to preserve stemness. Nat. Immunol. 22, 723–734 (2021). sourceExperimental — accuracy not yet measured
The cited paper’s PAK4-inhibition section (pp. 20–21) discusses hematopoietic stem-cell responses to treatment, not TGFB1 or fibrosis. Searches of our copy for TGFB1, TGF-beta, and myelofibrosis found no passage addressing the claimed role of TGF-beta in fibrotic-phase MPN. (LLM, conf=0.75)
boosteddirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Partly supported
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“We further incorporated cell hashing 24 that enabled multiplexing baseline and IFNa-treated samples into the same scRNA-seq reactions via time-point specifying barcoded antibodies, to obviate technical batch effects between serial samples ( Fig. 1b ).”
What the sources say
- Could not verifycites [24] Nam, A. S. et al. Somatic mutations and cell identity linked by genotyping of transcriptomes. Nature 571, 355–360 (2019). sourceExperimental — accuracy not yet measured
The Methods section on Genotyping of Transcriptomes describes cell barcodes used to link genotypes with transcriptomes, not antibody-based cell hashing. Searches for cell hashing, time-point-specific barcoded antibodies, and baseline versus IFNa-treated sample multiplexing found no passage addressing the cited claim. (LLM, conf=0.76)
plaindirectn = 5- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
- Could not verify
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“We identified that the IGP-specific gene signature was highly specific to neutrophils, providing evidence against a general inflammatory signature and further supporting the predicted lineage fate ( Fig. 1i ).”
What the sources say
- Could not verifycites [38] Rodriguez-Meira, A. et al. Unravelling intratumoral heterogeneity through high-sensitivity single-cell mutational analysis and parallel RNA sequencing. Mol. Cell 73, 1292–1305 (2019). sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 2 unverifiable. Expand the claim to see per-atom verdicts.
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Could not verify
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“TWIST1 has been implicated in mediating the downregulation of TNFa upon type 1 IFN treatment 53”
What the sources say
- Could not verifycites [53] Rodriguez-Meira, A. et al. Single-cell multi-omics identifies chronic inflammation as a driver of TP53-mutant leukemic evolution. Nat. Genet. 55, 1531–1541 (2023). sourceExperimental — accuracy not yet measured
The Results section, “Inflammation promotes TP53-associated clonal dominance” (page unavailable), reports reduced TNFα-associated gene signatures alongside increased IFN-response genes in TP53-mutant cells, explicitly without concurrent IFN treatment. Searches for TWIST1 and type I IFN-mediated TNFα downregulation found no passage in our copy linking TWIST1 to that effect. (LLM, conf=0.76)
hedgedconditional- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Could not verify
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“as other RFX members have been demonstrated to regulate MHC class II expression 35,64”
What the sources say
- Could not verifycites [35] Triana, S. et al. Single-cell proteo-genomic reference maps of the hematopoietic system enable the purification and massive profiling of precisely defined cell states. Nat. Immunol. 22, 1577–1589 (2021). sourceExperimental — accuracy not yet measured
The Results passages on surface markers and immune-cell populations do not discuss RFX proteins regulating MHC class II expression. Searches of our copy for RFX members and MHC class II regulation returned no passage addressing the claim. (LLM, conf=0.73)
- Could not verifycites [64] Li, X. Y. et al. The role of chromatin accessibility in directing the widespread, overlapping patterns of Drosophila transcription factor binding. Genome Biol. 12, R34 (2011). sourceExperimental — accuracy not yet measured
Our copy’s Discussion addresses chromatin accessibility and transcription-factor binding in Drosophila, not regulation of MHC class II expression. Searches for RFX, MHC class II, and major histocompatibility complex found no passage addressing the claim. (LLM, conf=0.75)
boosteddirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Could not verify
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“we incorporated time-point specifying barcoded antibodies 24 to combine serial samples from the same individuals into a single experiment to remove technical batch effects”
What the sources say
- Could not verifycites [24] Nam, A. S. et al. Somatic mutations and cell identity linked by genotyping of transcriptomes. Nature 571, 355–360 (2019). sourceExperimental — accuracy not yet measured
The Methods sections on GoT and Circularization GoT describe cell barcodes, sample indexes, and barcoded cDNA, but not time-point-specific barcoded antibodies. A search for antibody-based labeling of serial samples and removal of batch effects found no passage in our copy addressing that procedure. (LLM, conf=0.74)
plaindirectn = 4- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
- Could not verify
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“These individual datasets, together with the baseline ET samples from our previous work 20 , were integrated and underwent batchcorrection within Seurat”
What the sources say
- Partly supportedcites [20] Pourcelot, E. et al. Cytokine profiles in polycythemia vera and essential thrombocythemia patients: clinical implications. Exp. Hematol. 42, 360–368 (2014). sourceExperimental — accuracy not yet measured
The Patients and sample preparation section (page unavailable) reports samples from 21 patients with essential thrombocythemia, supporting the citation’s identification of earlier ET samples. But the paper describes plasma cytokine measurements, not baseline ET datasets that could be integrated in Seurat; its Statistical analysis section (page unavailable) names other software and does not describe batch correction. (LLM, conf=0.78)
- Not checked — no full text of the sourcecites [84] Feng, R. et al. PU.1 and C/EBPalpha/beta convert fibroblasts into macrophage-like cells. Proc. Natl Acad. Sci. USA 105, 6057–6062 (2008). source
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. It may state two separate claims as one.
- Partly supported
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“M131I, predicted to impact protein structure 61”
What the sources say
- Could not verifycites [61] Notta, F. et al. Distinct routes of lineage development reshape the human blood hierarchy across ontogeny. Science 351, aab2116 (2016). sourceExperimental — accuracy not yet measured
The Discussion passage concerns molecular markers of blood-cell lineage differentiation, not the M131I variant or its effect on protein structure. Searches for “M131I” and protein-structure predictions found no passage addressing the claim in our copy. (LLM, conf=0.75)
plainSingle case- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Could not verify
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“As nuclear hashing is known to be noisy 89 the nuclear hashing data was used in combination with cell clustering data, as the cells cluster based on treatment status.”
What the sources say
- Could not verifycites [89] Elf, S. et al. Mutant calreticulin requires both its mutant C-terminus and the thrombopoietin receptor for oncogenic transformation. Cancer Discov. 6, 368–381 (2016). sourceExperimental — accuracy not yet measured
The Methods passages describe cell lines, flow cytometry, and statistical analysis, but do not address nuclear hashing or its reliability. Further searches for “nuclear hashing” and its use with cell clustering found no passage on that point; page numbers were not available in our copy. (LLM, conf=0.76)
boosteddirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Could not verify
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“Only UMIs with at least 2 or more supporting reads were retained for final genotyping assignments, after the UMI collapse algorithm 42,86 .”
What the sources say
- Could not verifycites [42] Lin, Q., Dong, C. & Cooper, M. D. Impairment of T and B cell development by treatment with a type I interferon. J. Exp. Med. 187, 79–87 (1998). sourceExperimental — accuracy not yet measured
The Materials and Methods section describes flow cytometry of mouse cells, not UMI-based sequencing or genotyping. Searches for UMI collapse, supporting-read thresholds, and genotyping assignments found no passage addressing the claimed two-read rule; page numbers are unavailable in our copy. (LLM, conf=0.78)
- Could not verifycites [86] Kondo, M., Weissman, I. L. & Akashi, K. Identification of clonogenic common lymphoid progenitors in mouse bone marrow. Cell 91, 661–672 (1997). sourceExperimental — accuracy not yet measured
The paper’s Experimental Procedures (page unavailable) describe cell sorting and PCR to detect TCRβ and IgH rearrangements. Searches for UMIs, a UMI-collapse algorithm, and a two-read threshold found no passage addressing the claimed genotyping rule. (LLM, conf=0.76)
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Could not verify
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Gene set enrichment analysis identified the upregulation of TNFa via NFKB pathway (Adj. P-val = 3.5 x 10 -8 , Hallmark), and downregulation of the MYC targets (Adj. P-val = 6.8 x 10 -6 , Hallmark, Fig. 1e right, Supplementary Table 4 ).”
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“IFNa also induced a significant expansion of the lymphoid progenitors, especially large Pre-B and small Pre-B cells, and diminution of the megakaryocytic-erythroid lineage progenitors, namely MkPs, erythroid progenitors (EP), and megakaryocytic-erythroid progenitors (MEP; Fig. 2b,c; fold change of cell frequencies from serial samples in Fig. 2d ).”
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“MPO , a neutrophil-specific gene, and CSF3R , encoding the G-CSF receptor, were upregulated while the MHC class II genes ( CD74, HLA-DRA, HLA-DPA1, HLA-DRB1, HLADPB1 ) were downregulated, further providing evidence for its differentiation into a neutrophilic lineage versus monocytic or dendritic cell lineages ( Fig. 1h, Supplementary Table 3 ).”
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We also observed an increase in the proportion of CD34 + , TdT + , CD19 + cells of total viable cells analyzed, as well as an increase in the CD34 -, TdT -, CD19 + B-lymphocytes ( Fig. 2f) , providing evidence for an active expansion of the lymphoid progenitors, rather than simply a proportional increase due to diminution of the megakaryocytic-erythroid lineage cells.”
plaindirectn = 9- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Of the interferon regulatory factors, IRF1 was upregulated in IGP compared to HSC1 ( Fig. 1h, Supplementary Table 3 ; both comparison groups under IFNa treatment) and IMP ( Fig. 1e, Supplementary Table 3 ), highlighting IRF1 as the key regulatory factor among other IFNa-induced TFs in IGP development.”
boosteddirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“To determine changes in gene expression that may drive the differentiation from HSC1 to IGPs, we compared IGPs to HSC1 and identified a reinforcement of the AP-1 and KLF family TF expression and downregulation of NR4A TFs ( Fig. 1g,h, Supplementary Table 3,4; notably, only IFNa-treated cells were included in the differential expression analysis to remove the treatment variable altogether).”
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Interferon regulatory factor 1 ( IRF1 ) was also upregulated ( Fig. 1e left, Supplementary Table 3 ), indicating that the cluster was associated with IFNa treatment.”
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Consistently, the HSC-specific IFNa-upregulated gene signature (data presented in Fig. 2j ) was significantly downregulated in the IGPs compared to the HSCs while the IFNadownregulated genes were upregulated in the IGPs, with both cell groups under the same IFNa treatment ( Fig. 2m ).”
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Indeed, HSCs expressing high levels of CXCR4 gene were less likely to be in cell cycle and enriched for baseline cells (P < 2.2 x 10 -22 , Fisher exact test) and conversely, HSCs in the cell cycle did not express high CXCR4 gene expression ( Supplementary Fig. 4a ).”
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Projection of the cell identity assignments (as in Fig. 1c ) revealed that the cells clustered based on cell identity as well as based on treatment status ( Fig. 2a, Supplementary Fig. 3b ).”
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In an example case of patient IFN03 for whom three time points were available - (1) baseline, (2) treated for one year, and (3) treated for four years but off therapy for 3 weeks at time of collection - HSCs at year 1 displayed a striking transcriptional difference compared to baseline cells, whereas cells that have been off therapy for 3 weeks at year 4 were less distinct, consistent with a half-”
plaincorrelationalSingle case- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
- Rests on an assumption: The half-life of pegylated-IFNa is approximately 2 weeks.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Interestingly, most cell types also upregulated genes within the IFNg pathway, but not the IGPs ( Fig. 2k, Supplementary Table 6 ), consistent with a specific upregulation of type 1 interferon-associated IRF1 in the IGPs.”
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Upon IFNa therapy, the double-mutated clone overtook the neoplasm and the overall stem cell population”
plaindirectSingle case- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the HSC-specific IFNadownregulated gene signature was downregulated in the double mutant clone both at baseline and to a greater degree at treatment”
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“IFNa enhanced the activities of STAT2 and numerous interferon regulatory factors in HSCs, in contrast to the specific activity of IRF1 in IGPs”
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Rests on an assumption: Chromatin accessibility of TF binding sites is a reliable surrogate of TF activity.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the double mutant HSCs exhibited high expression of the HSC-specific IFNaupregulated gene signature (derived from data displayed in Fig. 2j ) at baseline and even higher upon IFNa therapy compared to baseline”
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“we observed no significant shifts in the relative proportion, except in one patient IFN04 whose clone expanded significantly upon IFNa therapy”
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These clusters were collapsed into 15 main progenitor subsets based on expression of levels of these canonical markers ( Supplementary Fig. 2a,b ).”
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Genes highlighted in blue-green are enriched in the TNFa signaling via NFKB and those in blue enriched in the IFNa/g response”
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the motif RFX8, known to positively regulate MHC class II expression was present in the positively regulating peaks, but not in the negatively regulating loci”
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Rests on an assumption: Chromatin accessibility of TF binding sites is a reliable surrogate of TF activity.
In the paper
“We determined TF motifs present in the regulatory peaks that correlated with RFX3 gene expression (i.e. linked peaks analysis) 63 and identified those of STAT2 and IRF1 (further supporting an IRF1-specific response) as well as FOSB and SPI1 (or PU.1), which were differentially upregulated at the gene expression level in IGPs”
What the sources say
- Not checked — no full text of the sourcecites [63] Lee, T. I. et al. Transcriptional regulatory networks in Saccharomyces cerevisiae. Science 298, 799–804 (2002). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Rests on an assumption: Chromatin accessibility of TF binding sites is a reliable surrogate of TF activity.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“IFNa induces lymphoid differentiation and downregulation of TNFa and TGFb signaling.”
- Also stated in: § Competing interests · plain
“Downregulation of TNF-a and TGFb signaling are also observed in the HSCs upon IFNa treatment.”
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Also stated in: § Competing interests · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Moreover, IFNa induced proliferation to a greater degree in the mutated cells compared to wildtype cells within the myeloid progenitor compartment, but not the lymphoid, that is, it was restricted to the progenitor subsets in which the CALR -mutation induced proliferation at baseline ( Fig. 3e) .”
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the predominant signatures of the double mutant HSCs were decreased TNFa and TGFb signaling and upregulation of IFN response genes”
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“As IFNa induces cell cycle entry of mutated HSCs to a greater extent than wildtype HSCs”
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper may give no reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Genes positively regulated by RFX2/3 included MPO , consistent with neutrophilic differentiation, and genes involved in cell cycle entry”
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Rests on an assumption: Chromatin accessibility of TF binding sites is a reliable surrogate of TF activity.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Table with genes that are identified as being positively regulated by RFX2 and RFX3 using Gene-Peak cis-association .”
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We identified 35 clusters in the integrated data, which were annotated according to canonical lineage markers identified previously in single-cell RNAseq data of normal hematopoietic progenitor cells 27 .”
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These peaks included motifs for IRF1 and STAT2 as well as immediate response factors including AP-1 and KLF families, but not RFX2/3”
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Rests on an assumption: Chromatin accessibility of TF binding sites is a reliable surrogate of TF activity.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“These methods allow us to overlay two hematopoietic differentiation landscapesone mutated and the other wildtype-from the same individual, thus enabling a direct comparison between mutated and wildtype cells, before and after treatment.”
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“MPNs are often driven by a single somatic mutation in CALR , JAK2 or MPL , and thus provide an informative model of an early clonal process within the hematopoietic system 18 .”
What the sources say
- Not checked — no full text of the sourcecites [18] Neurath, M. F. Cytokines in inflammatory bowel disease. Nat. Rev. Immunol. 14, 329–342 (2014). source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“IFNa remains a highly effective therapy for MPN, frequently resulting in the normalization of the patients' blood counts and even molecular response (i.e. reduction in variant allele frequencies), with evidence suggesting that IFNa may deplete clonal stem cells via induction of HSCs into cell cycle entry and exhaustion 12,18 .”
What the sources say
- Not checked — no full text of the sourcecites [12] Rao, T. N. et al. JAK2-V617F and interferon-α induce megakaryocyte-biased stem cells characterized by decreased long-term functionality. Blood 137, 2139–2151 (2021). source
- Not checked — no full text of the sourcecites [18] Neurath, M. F. Cytokines in inflammatory bowel disease. Nat. Rev. Immunol. 14, 329–342 (2014). source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“We therefore leveraged single-cell multi-omics platforms that detect the mutation status and whole transcriptomes with immunophenotyping or chromatin accessibility data, within the same thousands of cells.”
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, given the induction of the IGP differentiation, these findings suggest that IFNa is able to induce both a pro-inflammatory state via IGP differentiation and an antiinflammatory state via differentiation shifts toward lymphoid development and downregulation of TNFa and NFKB activities - both occurring in parallel within the same individual's hematopoiesis.”
hedgeddirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Furthermore, as the IGPs constitute a small minority of the progenitors (<1%), IGPs are not likely to contribute significantly to overall neutrophil pool during IFNa therapy, consistent with the absence of neutrophilia in patients treated with IFNa.”
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Patients treated with IFNa do not develop neutrophilia.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The study was conducted in accordance with the Declaration of Helsinki protocol,”
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“To remove the noise from the counts matrix data, any cell with intensity less than 50 for DAPI and auto-fluorescence markers was excluded from the analysis.”
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“GoT-IM captures genotyping, immunophenotyping, and whole transcriptomes in thousands of CD34 + cells at baseline and treatment with IFNa.”
plainn = 49,891- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
In the paper
“To eliminate experimental batch effects, cells were labelled simultaneously with hashing antibodies with timepoint-identifying barcodes as described 15”
What the sources say
- Not checked — no full text of the sourcecites [15] Franceschi, C. et al. Inflamm-aging. An evolutionary perspective on immunosenescence. Ann. N. Y. Acad. Sci. 908, 244–254 (2000). source
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, the proliferative effects of IFNa appeared to be compounded by those of the underlying CALR mutation; in other words, the mutated cells were primed toward a greater proliferative response upon IFNa treatment.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The thresholds were manually set for each marker based on examination by a board-certified hematopathologist.”
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“batch-correction was perfomed with runHarmony (Harmony, v0.1.0) which iteratively learns cell-specific linear correction function to account for batch effect.”
What the sources say
- Not matchedcites Harmony, v0.1.0
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. The quote only partly states this claim.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“PU.1 also mediates skewing of hematopoiesis toward the lymphoid lineage via co-activity with TCF3 and toward the granulo-monocytic lineage, especially in the mutated cells, via CEBPA.”
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“and all patients provided informed consent.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In a minority population of HSCs with high RFX2/3 and AP-1 activities at baseline, PU.1 and IRF1 induce their differentiation into the IGPs, associated with high TNFa signaling.”
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“For the RNA data, cells with UMI > or < 3 standard deviations from the mean UMI or mitochondrial gene percentage > 25%, were filtered.”
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Retrospective flow cytometry data analysis was performed in accordance with relevant guidelines, regulations and approval by the Institutional Review Board at Weill Cornell Medicine (IRB #1007011151).”
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These findings identified the immediate response factors and IRF1/STAT2 as negative regulators of MHC class II genes across cell types, while RFX2/3 was highly specific for MHC class II downregulation during IGP differentiation.”
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Chromatin accessibility of TF binding sites is a reliable surrogate of TF activity.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The study was approved by the local ethics committee and by the Institutional Review Board (IRB) of Weill Cornell Medicine.”
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Cells in which both barcodes are detected are considered as doublets and excluded.”
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“We orthogonally validated that IFNa induced greater proliferative rates in the myeloid progenitors by performing multiplexed in situ fluorescent imaging of bone marrow paraffin-embedded sections from patients with CALR mutations with or without IFNa treatment (n = 5 with no IFNa, n = 4 with IFNa, Fig. 3f, left ).”
plaindirectn = 5- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Cells with blacklist ratio >0.02, TSS enrichment <2 and nucleosome signal >4 were filtered out.”
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“cells with UMI > or < 3 standard deviations from the mean UMI or mitochondrial gene percentage > 10%, were filtered (Supplementary Figure 1a)”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The activities of cell lineage specifying TF were consistent with the cell type assignments”
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Only IFNa-treated cells were included in the DE analysis to remove the treatment variable altogether.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The quote only partly states this claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“genotyping efficiency was significantly lower in GoT-ATAC compared to GoT-IM, due to the limited transcript pool in the nucleus versus whole cell”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, RFX2/3 and AP-1 TFs positively regulated the expression of one another, synergizing the IGP development.”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Chromatin accessibility of TF binding sites is a reliable surrogate of TF activity.
The paper relies on this without support.
The study of cytokines in human hematopoiesis is challenging due to the concerted activities of multiple cytokines across physiologic and pathologic processes.
“However, the study of cytokines in human hematopoiesis is challenging due to the concerted activities of multiple cytokines across physiologic and pathologic processes.”
The paper relies on this without support.
HSC-enriched bone marrow biopsies are rare, as they are restricted to patients with suspected or diagnosed hematopoietic neoplasms or defects.
“Moreover, HSC-enriched bone marrow biopsies are rare, as they are restricted to patients with suspected or diagnosed hematopoietic neoplasms or defects.”
The paper relies on this without support.
The molecular effects undergirding the clinical improvements of CALR-mutated MPN through IFNa therapy remain an open arena of investigations.
“Thus, the molecular effects undergirding the clinical improvements of CALR -mutated MPN through IFNa therapy remain an open arena of investigations.”
The paper relies on this without support.
The mutated cells are not distinguishable from the admixed wildtype cells by cell surface markers.
“While MPNs provide a useful model to study the effects of somatic mutations on human hematopoiesis, the precise examination of IFNa effects on mutated versus wildtype blood formation is challenging because the mutated cells are not distinguishable from the admixed wildtype cells by cell surface markers.”
The paper relies on this without support.
The half-life of pegylated-IFNa is approximately 2 weeks.
“consistent with a half-life of the pegylated-IFNa of ~2 weeks”
The paper relies on this without support.
Patients treated with IFNa do not develop neutrophilia.
“consistent with the absence of neutrophilia in patients treated with IFNa.”
The paper relies on this without support.
Chromatin accessibility of TF binding sites is a reliable surrogate of TF activity.
“Chromatin accessibility enables approximation of TF activity based on accessibility of the TF binding sites.”
“as a reliable surrogate of TF activities”
The paper relies on this without support.
MPN presents primarily as a defect in homeostatic hematopoietic development, due to abnormal differentiation skewing and increased proliferation of one or more myeloid lineages.
“MPN presents primarily as a defect in homeostatic hematopoietic development, due to an abnormal differentiation skewing and increased proliferation of one or more of the myeloid lineages”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Competing interests
“DE genes identified using linear mixed modeling with/without treatment status.”
§ Supplementary Information
“Supplementary Table 7 (related to Fig. 3h). Differential gene expression analysis between single mutant and double mutant HSCs from IFN04 at baseline was performed via logistic regression framework.”
Citations
Cites
Items 201–208 of 208
Nam, A. S., Dusaj, N. N., Izzo, F., Murali, R., Myers, R. M., Mouhieddine, T. H., Sotelo, J., Benbarche, S., Waarts, M. R., Gaiti, F., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.01.14.476225 · Cited by 10
Self-citationHuman haematopoietic stem cells remember inflammatory stress
Zeng, A. G. X., Nagree, M. S., Jakobsen, N. A., Shah, S., Varesi, A., Kang, J. R. W., Murison, A., Cheong, J.-G., Turkalj, S., Zhang, X., et al. (2026) · Nature · doi:10.1038/s41586-026-10522-7 · Cited by 10
Self-citationAnnaNamLab/Type1_IFN_Perturbs_Clonal_Competition: Release for Zenodo
AnnaNamLab, & Chhiring-Lama (2026) · Zenodo (CERN European Organization for Nuclear Research) · doi:10.5281/zenodo.21630099 · Cited by 1
SimonsonLab/2022_MPN_interferon_manuscript: zenodo_release3
Simonson, P. D. (2026) · Zenodo (CERN European Organization for Nuclear Research) · doi:10.5281/zenodo.21697793 · Cited by 1
Self-citationPU.1 enforces quiescence and limits hematopoietic stem cell expansion during inflammatory stress
Chavez, J. S., Rabe, J. L., Loeffler, D., et al. (2020) · doi:10.1101/2020.05.18.102830 · Cited by 1
VIPS - a highly tuned image processing software architecture
Martinez, K., & Cupitt, J. (2005) · IEEE International Conference on Image Processing 2005 · doi:10.1109/icip.2005.1530120
SimonsonLab/2022_MPN_interferon_manuscript: zenodo_release3
Simonson, P. D. (2026) · Zenodo · doi:10.5281/zenodo.21697794
Self-citationAnnaNamLab/Type1_IFN_Perturbs_Clonal_Competition: Release for Zenodo
AnnaNamLab, & Chhiring-Lama (2026) · Zenodo · doi:10.5281/zenodo.21630100
Cited by
Sorted by citations
Lyadova, I. V. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1717370 · Cited by 2
Varesi, A., Nagree, M. S., Biasio, I. D., Zeng, A. G. X., Shah, S., Kim, H., Zhang, M., Murison, A., Dick, J. E., & Xie, S. Z.-J. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.06.11.659017 · Cited by 1
Interferon-α directs hematopoietic stem cells toward competing fates
Rodriguez-Meira, A. (2026) · Nature Genetics · doi:10.1038/s41588-026-02797-3
Metadata
- Authors
- Lama, C., Isakov, D., Rosenberg, S., Quijada-Álamo, M., Saurty-Seerunghen, M. S., Moein, S., Nozais, M., Abera, T.-A., Sakaguchi, O., Totwani, M., Freed, G., Zaydon, L., Poon, C.-L., Parghi, N., Kubas-Meyer, A., Xie, A. X., Omar, M., Choi, D., Castillo-Tokumori, F., Abu-Zeinah, G., Dillard, A., Ganesan, S., Omans, N. D., Dusaj, N., Chamely, P., Mimitou, E., Smibert, P., Kosiorek, H. E., Dueck, A. C., Weinberg, R., Chaligne, R., Marcellino, B., Marchionni, L., Patel, S., Simonson, P., Landau, D. A., Wagenblast, E., Hoffman, R., & Nam, A. S.
- Affiliations
- Weill Cornell Medicine (US)
- Memorial Sloan Kettering Cancer Center (US)
- Icahn School of Medicine at Mount Sinai (US)
- Cedars-Sinai Medical Center (US)
- New York Genome Center (US)
- Immunai (United States) (US)
- 10X Genomics (United States) (US)
- Mayo Clinic in Arizona (US)
- Mayo Clinic (US)
- New York Blood Center (US)
- Tisch Cancer Institute (US)
- Corresponding author
- Nam, Anna S.
- ORCID
- Isakov, Danielle
- Rosenberg, Shira
- Saurty-Seerunghen, Mirca S.
- Nozais, Mathis
- Totwani, Mansi
- Freed, Grace
- Poon, Chi-Lam
- Parghi, Neelang
- Xie, Amy X.
- Choi, Daniel
- Castillo-Tokumori, Franco
- Abu-Zeinah, Ghaith
- Dillard, Alicia
- Ganesan, Saravanan
- Omans, Nathaniel D.
- Dusaj, Neville
- Mimitou, Eleni
- Smibert, Peter
- Kosiorek, Heidi E.
- Dueck, Amylou C.
- Weinberg, Rona
- Chaligne, Ronan
- Marcellino, Bridget
- Marchionni, Luigi
- Patel, Sanjay
- Simonson, Paul
- Landau, Dan A.
- Wagenblast, Elvin
- Hoffman, Ronald
- Nam, Anna S.
- Venue
- Nature Genetics
- Published
- 2026-09-15
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W7213233242
- Cited by
- 3
- References
- 178
- Citations by year
- 2026: 2
- FWCI
- 8.90
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Nature Genetics (publishedVersion, cc-by-nc-nd)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Burroughs Wellcome Fund
- National Institutes of Health (T32GM007739, 5t32gm152349-02, 5r01hl167139-03)
- Weill Cornell Medical College (T32GM007739)
- National Heart, Lung, and Blood Institute (F30HL156496)
- National Institute of General Medical Sciences (T32GM007739)
- Topics
- Health Sciences › Medicine › Hematology › Myeloproliferative Neoplasms: Diagnosis and Treatment
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Keywords
- type I interferon, interferon-alpha, clonal competition, clonal hematopoiesis, myeloproliferative neoplasms, hematopoietic stem cells, HSC differentiation, lymphoid differentiation, myeloid differentiation, somatic mutations, CALR mutation, JAK2 mutation, clonal fitness, inflammation, chromatin accessibility, cell cycle entry, blood count
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-28, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-28 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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