The DOI matches its Crossref record; 54 of the 54 references it cites were found in a registry or an index; 11 of the 46 sources its claims cite were checked for support.
Macrophage development from HSCs requires PU.1-coordinated microRNA expression
Open accessAbstract
The differentiation of HSCs into myeloid lineages requires the transcription factor PU.1. Whereas PU.1-dependent induction of myeloid-specific target genes has been intensively studied, negative regulation of stem cell or alternate lineage programs remains incompletely characterized. To test for such negative regulatory events, we searched for PU.1-controlled microRNAs (miRs) by expression profiling using a PU.1-inducible myeloid progenitor cell line model. We provide evidence that PU.1 directly controls expression of at least 4 of these miRs (miR-146a, miR-342, miR-338, and miR-155) through temporally dynamic occupation of binding sites within regulatory chromatin regions adjacent to their genomic coding loci. Ectopic expression of the most robustly induced PU.1 target miR, miR-146a, directed the selective differentiation of HSCs into functional peritoneal macrophages in mouse transplantation assays. In agreement with this observation, disruption of Dicer expression or specific antagonization of miR-146a function inhibited the formation of macrophages during early zebrafish (Danio rerio) development. In the present study, we describe a PU.1-orchestrated miR program that mediates key functions of PU.1 during myeloid differentiation.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
PU.1 directly coordinates a microRNA program during myeloid differentiation, including miR-146a, miR-342, miR-338, and miR-155. Ectopic miR-146a selectively drives HSC-derived peritoneal macrophages in mice, and miR-146a loss impairs macrophage development in zebrafish.
Key findings
- PU.1 induction in PUER cells changed 10 miRs upward and 10 downward; among up-regulated miRs, miR-146a increased 29.55-fold, miR-342 23.09-fold, miR-155 2.95-fold, and miR-338 2.08-fold.
- PU.1 occupied open chromatin near miR-146a, miR-342, miR-338, and miR-155; miR-146a, miR-342, and miR-338 showed sustained induction, whereas miR-155 was transient.
- Ectopic miR-146a expression in FACS-purified HSCs produced GFP-high donor cells exclusively in the peritoneum, with monocyte/macrophage markers CD11b, F4/80, CD115, and MHC-II and phagocytic activity; no such cells were detected in blood, spleen, BM, brain, liver, or lung.
- In zebrafish, MZdicer+430 embryos had profoundly reduced L-plastin+ macrophages, and miR-146a knockdown caused a selective loss of myeloid but not erythroid cells.
Methods
- PU.1-inducible PUER myeloid progenitor cells and PU.1 KO controls were profiled for 189 miRs by real-time PCR; differentially expressed miRs were identified by SAM with ≥2-fold up or ≤0.75-fold down and q<5%.
- PU.1 binding was mapped by ChIP-seq and DNase hypersensitivity in PUER cells and primary macrophages; miR-146a regulation was tested by luciferase reporter assays with wild-type or mutated PU.1-binding motif and by PU.1 shRNA in RAW264.7 cells.
- Adult HSC function was tested by transplanting GFP-tagged miR-146a- or control-transduced LSK cells into irradiated SJL CD45.1 recipients; zebrafish experiments used Dicer mutants, antisense oligonucleotide knockdown, whole-mount in situ hybridization for L-plastin, and FACS.
Limitations
- The paper states that the molecular mechanism by which miR-146a drives peritoneal macrophage differentiation “is still unclear,” and that enhanced phagocytosis observed in miR-146a-induced monocytes “will require further investigation.”
- The paper notes that macrophages express more miR-146a than granulocytes despite comparable PU.1 levels, suggesting “as-yet-unknown additional regulatory factors” in macrophages.
- Evident from the text: the adult in vivo gain-of-function result is restricted to peritoneal macrophages, and the zebrafish miR-146a loss-of-function uses antisense knockdown rather than a genetic miR-146a mutant.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
50 Own result · 28 Own interpretation · 13 No full text of the sources · 8 Not checked yet · 3 Partly supported · 2 Supported so far · 2 No basis given · 1 Mixed support · accuracy not yet measured
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“In addition to miRs with thus-far-unknown functions in hematopoietic cells, we identified several miRs with previously reported (partly controversial) roles in myelopoiesis and/or leukemia as regulated by PU.1.10,16,[46][47][48]”
§ Macrophage development from HSCs requires PU.1-coordinated microRNA expression > Discussion
What the sources say
- Supportedcites [10] Fazi, 2005, A minicircuitry comprised of microRNA-223 and transcription factors NFI-A and C/EBPalpha regulates human granulopoiesis., Cell source
The Discussion identifies miR-223 as a modulator of human myeloid differentiation, and the Summary reports that changing its expression affects differentiation in acute promyelocytic leukemia cells. This supports the cited paper as evidence for a previously reported role of a miRNA in myelopoiesis and leukemia; the citing authors' finding that PU.1 regulates the miRNAs is their own result. (LLM, conf=0.90)
- Could not verifycites [16] Taganov, 2006, NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses., Proc Natl Acad Sci U S A sourceExperimental — accuracy not yet measured
The Results report LPS-induced expression of miR-146, miR-155, and miR-132 in a monocytic leukemia cell line, but do not establish a role for those miRNAs in myelopoiesis or leukemia. Searches for PU.1 and for roles in myeloid differentiation or leukemia found no passage addressing the attributed point. (LLM, conf=0.72)
- Not checked — no full text of the sourcecites [46] Velu, 2009, Gfi1 regulates miR-21 and miR-196b to control myelopoiesis., Blood source
- Supportedcites [47] Romania, 2008, MicroRNA 155 modulates megakaryopoiesis at progenitor and precursor level by targeting Ets-1 and Meis1 transcription factors., Br J Haematol source
The Discussion reports that MIRN155 affects megakaryocyte differentiation and may play a role in normal myelopoiesis. This supports the cited paper as evidence of a previously reported role for a miRNA; the finding that the miRNAs are regulated by PU.1 is the citing authors’ own, not attributed to this source. (LLM, conf=0.90)
- Supportedcites [48] O'Connell, 2008, Sustained expression of microRNA-155 in hematopoietic stem cells causes a myeloproliferative disorder., J Exp Med source
The Results report that sustained miR-155 expression in mouse hematopoietic stem cells caused a myeloproliferative disorder, and the Discussion links miR-155 to myeloid-cell expansion and notes its enhanced expression in some AML patients. This supports citing the paper for a previously reported role of miR-155 in myelopoiesis and/or leukemia. The statement that PU.1 regulates the miRs is the citing authors’ own finding, not a finding attributed to this source. (LLM, conf=0.90)
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.
- Supported
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 contrast, the expression of miR-155 transiently increased at 1 and 3 days, but decreased afterward in differentiated macrophages at day 7 after induction.”
§ Macrophage development from HSCs requires PU.1-coordinated microRNA expression > PU.1 controls microRNA expression with different kinetics
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.
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
“Among the increased miRs were 6 that had not been attributed to myeloid differentiation before (miR-409, miR-434-5p, miR-096, miR-151, miR-33, and miR-485-5p).”
§ Macrophage development from HSCs requires PU.1-coordinated microRNA expression > Identification of a PU.1-dependent myeloid microRNA profile
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.
- Based: passes — The paper gives a 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
“Four of the PU.1-up-regulated miRs (miR-146a, miR-342, miR-338, and miR-155) fulfilled these criteria (Figure 2A).”
§ Macrophage development from HSCs requires PU.1-coordinated microRNA expression > Dynamic PU.1 binding near genomic loci encoding microRNAs
plaincorrelational- 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.
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
“expression of miR-146a, miR-342, and miR-338 steadily increased during differentiation of PUER cells and peaked in terminally differentiated macrophages (Figure 2B).”
§ Macrophage development from HSCs requires PU.1-coordinated microRNA expression > PU.1 controls microRNA expression with different kinetics
plaincorrelational- 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.
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 provide evidence that PU.1 directly controls expression of at least 4 of these miRs (miR-146a, miR-342, miR-338, and miR-155) through temporally dynamic occupation of binding sites within regulatory chromatin regions adjacent to their genomic coding loci.”
- Also stated in: § Introduction · plain
“Unbiased mapping of PU.1 binding (ChIPseq) and locus accessibility (DNase hypersensitivity) in PUER cells and primary macrophages revealed that the expression of 4 miRs (miR-146a, miR-342, miR-338, and miR-155) is PU.1 dependent during the earliest steps of myeloid progenitor maturation.”
§ Macrophage development from HSCs requires PU.1-coordinated microRNA expression > Abstract
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.
- Also stated in: § Introduction · 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
“Ectopic expression of the most robustly induced PU.1 target miR, miR-146a, directed the selective differentiation of HSCs into functional peritoneal macrophages in mouse transplantation assays.”
- Also stated in: § Introduction · boosted
“We demonstrate that, functionally, miR-146a fulfills a surprisingly selective role during adult myelopoiesis in that its ectopic expression specifically drives the replenishment of peritoneal macrophages from HSCs in vivo.”
- Also stated in: § MiR-146a drives selective differentiation of adult HSCs into peritoneal macrophages in vivo · boosted
“In summary, enforced expression of miR-146a drives HSCs to selectively mature into peritoneal macrophages during adult hematopoiesis.”
§ Macrophage development from HSCs requires PU.1-coordinated microRNA expression > Abstract
boosteddirect- 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.
- Also stated in: § Introduction · boosted
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
“Profiling the early maturation stage of myelopoiesis in a PU.1-inducible cell line (PUER) yielded such miR candidates.”
§ Macrophage development from HSCs requires PU.1-coordinated microRNA expression > Introduction
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.
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 a conserved DNAse HSS that harbored a strong PU.1-binding peak at 10 kb upstream (Ϫ10 kb) of the pre-miR-146a locus.”
§ Macrophage development from HSCs requires PU.1-coordinated microRNA expression > Dynamic PU.1 binding near genomic loci encoding microRNAs
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.
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
“Regulation of miR-146a operates through a conserved PU.1-binding motif at 10 kb upstream of the miR-146 genomic locus.”
§ Macrophage development from HSCs requires PU.1-coordinated microRNA expression > Discussion
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. 18
- It may state two separate claims as one. 38
Some cited sources support this claim and some don’t — read each source’s verdict below.
In the paper
“Mir-146a expression has been shown to be inducible on activation in a set of mature hematopoietic cells, namely in T cells, 50 dendritic cells, 38 and macrophages.16”
§ Macrophage development from HSCs requires PU.1-coordinated microRNA expression > Discussion
What the sources say
- Not checked — no full text of the sourcecites [50] Curtale, 2010, An emerging player in the adaptive immune response: microRNA-146a is a modulator of IL-2 expression and activation-induced cell death in T lymphocytes., Blood source
- Disputedcites [38] Jurkin, 2010, miR-146a is differentially expressed by myeloid dendritic cell subsets and desensitizes cells to TLR2-dependent activation., J Immunol sourceExperimental — accuracy not yet measured
The citation is attached to the dendritic-cell part of the sentence. In the section ‘miR-146a is expressed at high levels in nonactivated LCs’ (page unavailable), the paper reports that activation did not increase miR-146a expression in Langerhans cells, a dendritic-cell subset; the Discussion contrasts their constitutive expression with activation-induced expression in monocytes. (LLM, conf=0.88)
Checked by a reasoning model — may be wrong.
- Partly supportedcites [16] Taganov, 2006, NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses., Proc Natl Acad Sci U S A sourceExperimental — accuracy not yet measured
Citation 16 is attached to the macrophage part of the sentence. The Results report LPS-induced miR-146a expression in THP-1 and HL-60 myeloid cell lines, with comparable induction in other myeloid lines, but do not establish it in mature macrophages. The T-cell and dendritic-cell clauses have separate citations and are not judged here. (LLM, conf=0.86)
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.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“MicroRNAs (miRs) are a class of small, noncoding, regulatory RNAs that repress gene expression posttranscriptionally, 7 which may have effects on lineage development.8”
§ Macrophage development from HSCs requires PU.1-coordinated microRNA expression > Introduction
What the sources say
- Supportedcites [7] Lagos-Quintana, 2002, Identification of tissue-specific microRNAs from mouse., Curr Biol source
Citation 8 is attached to the claim that miRNAs may affect lineage development. The paper’s Abstract says tissue-specific miRNA expression suggests a role in tissue specification or cell lineage decisions, matching that hedged claim. (LLM, conf=0.93)
- Not checked — no full text of the sourcecites [8] Chen, 2004, MicroRNAs modulate hematopoietic lineage differentiation., Science source
hedgedconditional- 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. It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“This region has been shown to contain a functional NF-B-binding site and also to bind PU.1.16,38”
§ Macrophage development from HSCs requires PU.1-coordinated microRNA expression > Dynamic PU.1 binding near genomic loci encoding microRNAs
What the sources say
- Partly supportedcites [16] Taganov, 2006, NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses., Proc Natl Acad Sci U S A sourceExperimental — accuracy not yet measured
The Results report that the miR-146a promoter’s LPS responsiveness depends on NF-κB-binding sites in an upstream 550-bp region. They do not identify those sites as being in the −10-kb region relative to pre-miR-146a or report PU.1 binding there. (LLM, conf=0.86)
- Not checked yetcites [38] Jurkin, 2010, miR-146a is differentially expressed by myeloid dendritic cell subsets and desensitizes cells to TLR2-dependent activation., J Immunol source
Checked before — its earlier verdict is held back until a new check runs.
plaincorrelational- 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.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“miR-223 was reported to direct granulocytic development, 10 although this has been questioned using knockout (KO) studies in mice.11,12”
§ Macrophage development from HSCs requires PU.1-coordinated microRNA expression > Introduction
What the sources say
- Supportedcites [10] Fazi, 2005, A minicircuitry comprised of microRNA-223 and transcription factors NFI-A and C/EBPalpha regulates human granulopoiesis., Cell source
The Discussion reports that miR-223 overexpression increased commitment to the granulocytic lineage, while knockdown had the opposite effect. The mouse knockout qualification is attributed to citations 11 and 12, not to this source. (LLM, conf=0.94)
- Not checked — no full text of the sourcecites [11] Johnnidis, 2008, Regulation of progenitor cell proliferation and granulocyte function by microRNA-223., Nature source
- Partly supportedcites [12] Fukao, 2007, An evolutionarily conserved mechanism for microRNA-223 expression revealed by microRNA gene profiling., Cell sourceExperimental — accuracy not yet measured
The Introduction describes an earlier report proposing a miR-223–transcription-factor circuit associated with human granulopoiesis. But this paper investigates what regulates miR-223 expression during myeloid differentiation; it does not establish that miR-223 directs granulocytic development. The mouse knockout qualification is attached to other citations, not this one. (LLM, conf=0.78)
hedgeddirect- 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. It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“This role is supported the very recent observation that miR-146a KO mice develop granulocytic hyperplasia and have a reduced macrophage compartment.51”
§ Macrophage development from HSCs requires PU.1-coordinated microRNA expression > Discussion
What the sources say
- Partly supportedcites [51] Boldin, 2011, miR-146a is a significant brake on autoimmunity, myeloproliferation, and cancer in mice., J Exp Med sourceExperimental — accuracy not yet measured
The Results section, “Massive myeloproliferation in miR-146a KO mice” (page unavailable), reports an expanding myeloid compartment dominated by CD11b+GR1+ blasts, supporting the granulocytic-expansion part of the claim. The Results section on M-CSF receptor (page unavailable) reports comparable macrophage colony formation in KO and wild-type marrow, not a reduced macrophage compartment. Our copy does not establish that the macrophage compartment is reduced. (LLM, conf=0.88)
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.
It may state two separate claims as one.
- Partly supported
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 agreement with this, no PU.1 occupancy was noted in mature macrophages, in which this site was also not accessible to DNase.”
§ Macrophage development from HSCs requires PU.1-coordinated microRNA expression > Dynamic PU.1 binding near genomic loci encoding microRNAs
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.
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
“Maximal PU.1 occupancy was reached at 1 hour after OHT induction, but declined steadily thereafter and was no longer detectable after 48 hours.”
§ Macrophage development from HSCs requires PU.1-coordinated microRNA expression > Dynamic PU.1 binding near genomic loci encoding microRNAs
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.
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 agreement with this observation, disruption of Dicer expression or specific antagonization of miR-146a function inhibited the formation of macrophages during early zebrafish (Danio rerio) development.”
- Also stated in: § Introduction · plain
“In agreement with this, a knock-down (KD) approach in zebrafish (Danio rerio) revealed a blood-specific requirement of miR-146a for macrophage development in the embryo, which is supported by the observation of diminished macrophage development in a Dicer-KO zebrafish model.”
§ Macrophage development from HSCs requires PU.1-coordinated microRNA expression > Abstract
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.
It may state two separate claims as one.
- Also stated in: § Introduction · 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
“In the present study, we show that miR-146a is dynamically expressed during adult hematopoiesis, and reveal that PU.1 is required to control this dynamic pattern in vitro and in vivo.”
§ Macrophage development from HSCs requires PU.1-coordinated microRNA expression > Introduction
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.
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
“MiR-342 is encoded in the third intron of the Evl gene (Enah/Vasp-like, NM_016337) 39 and we identified a PU.1-binding site 40 near the promoter region of the host gene (at 5 kb upstream of the transcription start site), which was increasingly occupied by PU.1 during PUER differentiation and was marked by a DNase HSS in mature macrophages.”
§ Macrophage development from HSCs requires PU.1-coordinated microRNA expression > Dynamic PU.1 binding near genomic loci encoding microRNAs
What the sources say
- Not checked — no full text of the sourcecites [39] Grady, 2008, Epigenetic silencing of the intronic microRNA hsa-miR-342 and its host gene EVL in colorectal cancer., Oncogene source
- Not checked — no full text of the sourcecites [40] De Marchis, 2009, A new molecular network comprising PU.1, interferon regulatory factor proteins and miR-342 stimulates ATRA-mediated granulocytic differentiation of acute promyelocytic leukemia cells., Leukemia source
plaincorrelational- 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.
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
“Moreover, PU.1 binding at this site was dynamic in that PU.1 occupancy increased with differentiation of PUER cells, and was strongest in fully matured PUER cells and in primary macrophages (Figure 2A top left panel).”
§ Macrophage development from HSCs requires PU.1-coordinated microRNA expression > Dynamic PU.1 binding near genomic loci encoding microRNAs
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.
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 detected PU.1 occupancy in the promoter region of the host gene (at 2 kb upstream) and more prominently within the first intron of Aatk, suggesting that PU.1 regulates miR-338 expression through these sites.Both sites are readily occupied during PUER induction and accessible to DNase in mature macrophages.”
§ Macrophage development from HSCs requires PU.1-coordinated microRNA expression > Dynamic PU.1 binding near genomic loci encoding microRNAs
hedgedcorrelational- 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.
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
“Using this strategy, we identified 10 miRs with increased expression and 10 miRs with decreased expression in the induced PUER cells compared with the controls.”
§ Macrophage development from HSCs requires PU.1-coordinated microRNA expression > Identification of a PU.1-dependent myeloid microRNA profile
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.
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 level of miR-146a expression in the retrovirally transduced cells was comparable to that detected in induced PUER cells and furthermore comparable to the extent of induction seen in macrophages derived from LSK cells.”
§ Macrophage development from HSCs requires PU.1-coordinated microRNA expression > MiR-146a drives selective differentiation of adult HSCs into peritoneal macrophages in vivo
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.
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
“All donor cells had a typical monocyte phenotype, as indicated by morphology and surface expression of the myelomonocytic markers CD11b, F4/80, CD115, and MHC-II, but lack of expression of the granulocyte marker Gr1, the T-cell marker CD3, and the B-cell marker B220 (Figure 4A-C and data not shown).”
§ Macrophage development from HSCs requires PU.1-coordinated microRNA expression > MiR-146a drives selective differentiation of adult HSCs into peritoneal macrophages in vivo
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.
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
“This effect lasted until 24 hours, but disappeared thereafter and was again undetectable at 48 hours.”
§ Macrophage development from HSCs requires PU.1-coordinated microRNA expression > Discussion
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.
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
“However, macrophages express more miR-146a as granulocytes, although both cell lineages express comparably high PU.1 levels.”
§ Macrophage development from HSCs requires PU.1-coordinated microRNA expression > Discussion
plaincorrelational- 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.
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
“PU.1 binding at the Bic gene, which hosts the miR-155 coding sequence, was not detectable in untreated PUER cells, but was induced within 1 hour of OHT stimulation.”
§ Macrophage development from HSCs requires PU.1-coordinated microRNA expression > Discussion
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.
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
“Whereas PU.1 occupancy and expression of miR-146a, miR-342, and miR-338 loci increased permanently with myeloid differentiation and peaked in terminally differentiated macrophages, miR-155 expression was induced by transient PU.1 occupancy.”
§ Macrophage development from HSCs requires PU.1-coordinated microRNA expression > Discussion
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.
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
“This experiment revealed basic transcription of miR-146a already in HSCs and myeloid progenitors, which increased markedly in mature myeloid cells (Figure 3A).”
§ Macrophage development from HSCs requires PU.1-coordinated microRNA expression > PU.1 is required for miR-146a expression in vivo
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.
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 comparison, specific KD of the unrelated control miR miR-430 had no effect on macrophage development, but caused several other previously reported morphological abnormalities, including dysmorphogenic brain and heart development such as underinflated brain ventricles, slight microcephaly, pericardial edema, and string-like hearts (data not shown).”
§ Macrophage development from HSCs requires PU.1-coordinated microRNA expression > For personal at Universiteitsbibliotheek Utrecht on September 29, 2011. bloodjournal.hematologylibrary.org From
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.
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
“Furthermore, zebrafish miR-146a shares the same seed region with its mouse and human homologs, suggesting conserved roles in these species (Figure 6A).”
§ Macrophage development from HSCs requires PU.1-coordinated microRNA expression > For personal at Universiteitsbibliotheek Utrecht on September 29, 2011. bloodjournal.hematologylibrary.org From
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.
None of the sources cited for this claim have been checked yet.
In the paper
“for example, miR-150 was shown to direct megakaryocyte-erythroid lineage fate 9”
§ Macrophage development from HSCs requires PU.1-coordinated microRNA expression > Introduction
What the sources say
- Not checked yetcites [9] Lu, 2008, MicroRNA-mediated control of cell fate in megakaryocyte-erythrocyte progenitors., Dev Cell source
Checked before — its earlier verdict is held back until a new check runs.
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.
- Not checked yet
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
“PU.1 is crucial for lymphomyeloid development, and its stage-specific expression is critical in preventing leukemic transformation.1,2”
§ Macrophage development from HSCs requires PU.1-coordinated microRNA expression > Introduction
What the sources say
- Not checked — no full text of the sourcecites [1] Rosenbauer, 2006, Lymphoid cell growth and transformation are suppressed by a key regulatory element of the gene encoding PU.1., Nat Genet source
- Not checked — no full text of the sourcecites [2] Scott, 1994, Requirement of transcription factor PU.1 in the development of multiple hematopoietic lineages., Science source
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. It may state two separate claims as one.
In the paper
“Whereas the differentiating effect of PU.1 in stem cells is attributed to target gene induction, targets of negative regulation have rarely been described.3”
§ Macrophage development from HSCs requires PU.1-coordinated microRNA expression > Introduction
What the sources say
- Not checked — no full text of the sourcecites [3] Weigelt, 2009, Transcriptomic profiling identifies a PU.1 regulatory network in macrophages., Biochem Biophys Res Commun source
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. 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
“This finding indicated that PU.1 binding to this site occurred early and increased progressively with differentiation into monocytic cells.”
§ Macrophage development from HSCs requires PU.1-coordinated microRNA expression > Dynamic PU.1 binding near genomic loci encoding microRNAs
hedgeddirect- 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.
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
“We conclude that PU.1 bound to open chromatin near 4 of its induced miR loci with 2 types of kinetics: (1) permanent (miR-146a, miR-342, and miR-338) and ( 2) transient (miR-155) during myeloid differentiation.”
§ Macrophage development from HSCs requires PU.1-coordinated microRNA expression > Dynamic PU.1 binding near genomic loci encoding microRNAs
boostedcorrelational- 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.
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
“This result suggested that PU.1 binding is needed to initiate the expression of miR-155, but not for its maintenance.”
§ Macrophage development from HSCs requires PU.1-coordinated microRNA expression > Dynamic PU.1 binding near genomic loci encoding microRNAs
hedgeddirect- 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.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“At a more global level, impairing mature miR expression by KO of the processing machinery in Dicer-KO experiments revealed miR dependency for HSCs 14 and osteoclast development.15”
§ Macrophage development from HSCs requires PU.1-coordinated microRNA expression > Introduction
What the sources say
- Not checked — no full text of the sourcecites [14] Guo, 2010, MicroRNA miR-125a controls hematopoietic stem cell number., Proc Natl Acad Sci U S A source
- Not checked yetcites [15] Sugatani, 2009, Impaired micro-RNA pathways diminish osteoclast differentiation and function., J Biol Chem source
Checked before — its earlier verdict is held back until a new check runs.
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.
In the paper
“The best-studied example of this type of negative regulation is the suppression of GATA1 activity by PU.1, which leads to a shift in cell fate toward the myeloid-lymphoid lineages.4”
§ Macrophage development from HSCs requires PU.1-coordinated microRNA expression > Introduction
What the sources say
- Not checked — no full text of the sourcecites [4] Zhang, 2000, PU.1 inhibits GATA-1 function and erythroid differentiation by blocking GATA-1 DNA binding., Blood source
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.
- 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.
In the paper
“Furthermore, down-regulation of the miR-17p-92 cluster can promote myeloid lineage fate.13”
§ Macrophage development from HSCs requires PU.1-coordinated microRNA expression > Introduction
What the sources say
- Not checked — no full text of the sourcecites [13] Fontana, 2007, MicroRNAs 17-5p–20a-106a control monocytopoiesis through AML1 targeting and M-CSF receptor upregulation., Nat Cell Biol 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.
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
“This discrepancy might be caused by the presence of as-yet-unknown additional regulatory factors in macrophages that cooperate with PU.1 to induce high-level miR-146a expression.”
§ Macrophage development from HSCs requires PU.1-coordinated microRNA expression > Discussion
hedgedconditional- 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
“It is therefore likely that PU.1 initiates the expression of miR-155 to escort quiescent HSCs into cycle and thus activates their initial differentiation into a transient amplifying myeloid progenitor stage.”
§ Macrophage development from HSCs requires PU.1-coordinated microRNA expression > Discussion
hedgeddirect- 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.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“This miR has been reported to stimulate granulopoiesis, 10 although controversy has been raised about this particular function.11,12”
§ Macrophage development from HSCs requires PU.1-coordinated microRNA expression > Discussion
What the sources say
- Not checked yetcites [10] Fazi, 2005, A minicircuitry comprised of microRNA-223 and transcription factors NFI-A and C/EBPalpha regulates human granulopoiesis., Cell source
Checked before — its earlier verdict is held back until a new check runs.
- Not checked — no full text of the sourcecites [11] Johnnidis, 2008, Regulation of progenitor cell proliferation and granulocyte function by microRNA-223., Nature source
- Not checked yetcites [12] Fukao, 2007, An evolutionarily conserved mechanism for microRNA-223 expression revealed by microRNA gene profiling., Cell source
hedgeddirect- 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. It may state two separate claims as one.
- Not checked yet
In the paper
“MiR-17p-92 is a direct target of c-MYC and can inhibit E2F to drive cellular proliferation.49”
§ Macrophage development from HSCs requires PU.1-coordinated microRNA expression > Discussion
What the sources say
- Not checked — no full text of the sourcecites [49] O'Donnell, 2005, c-Myc-regulated microRNAs modulate E2F1 expression., Nature 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. 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
“In summary, we describe herein a comprehensive PU.1orchestrated miR expression profile in which individual members can mediate the key functions of PU.1 to act on proliferation, induce myeloid differentiation, and suppress leukemic transformation.”
§ Macrophage development from HSCs requires PU.1-coordinated microRNA expression > Discussion
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.
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
“Therefore, our data indicate that PU.1 orchestrates the expression of an entire miR program necessary to guide correct differentiation and counteract malignant transformation of developing myeloid progenitors (supplemental Figure 3).”
§ Macrophage development from HSCs requires PU.1-coordinated microRNA expression > Discussion
hedgeddirect- 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.
It may state two separate claims as one.
- Rests on an assumption: PU.1 binding to genomic regions indicates direct transcriptional regulation.
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
“The expression pattern and function of PU.1 is highly conserved between zebrafish and mammals.44,45”
§ Macrophage development from HSCs requires PU.1-coordinated microRNA expression > For personal at Universiteitsbibliotheek Utrecht on September 29, 2011. bloodjournal.hematologylibrary.org From
What the sources say
- Not checked — no full text of the sourcecites [44] Bennett, 2001, Myelopoiesis in the zebrafish, Danio rerio., Blood source
- Not checked — no full text of the sourcecites [45] Lieschke, 2002, Zebrafish SPI-1 (PU.1) marks a site of myeloid development independent of primitive erythropoiesis: implications for axial patterning., Dev Biol 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.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“to delineate PU.1-dependent miRs showed a limited number of miR candidates, of which the miR-23 cluster was shown to block lymphopoiesis; however, that study did not clarify a specific myeloid profile.42”
§ Macrophage development from HSCs requires PU.1-coordinated microRNA expression > Discussion
What the sources say
- Not checked yetcites [42] Kong, 2010, MIR-23A microRNA cluster inhibits B-cell development., Exp Hematol source
Checked before — its earlier verdict is held back until a new check runs.
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. It may state two separate claims as one.
- Not checked yet
In the paper
“This decrease in PU.1 causes a severe hematopoietic phenotype with a differentiation block in myelopoiesis and, as a consequence, the development of acute myeloid leukemia.”
§ Macrophage development from HSCs requires PU.1-coordinated microRNA expression > PU.1 is required for miR-146a expression in vivo
What the sources say
- Not checked — no full text of the sourcecites [41] Rosenbauer, 2004, Acute myeloid leukemia induced by graded reduction of a lineage-specific transcription factor, PU.1., Nat Genet source
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.
It may state two separate claims as one.
In the paper
“However, many of these develop-mental defects are overcome by supplementing the mutant embryos with mature miR-430 (MZdicer ϩ430 ), which allows normal early development.26”
§ Macrophage development from HSCs requires PU.1-coordinated microRNA expression > Macrophage development requires microRNA expression
What the sources say
- Not checked — no full text of the sourcecites [26] Giraldez, 2005, MicroRNAs regulate brain morphogenesis in zebrafish., Science source
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.
It may state two separate claims as one.
In the paper
“Embryos of this model lack miR-processing capacity from the one-cell stage on, and as a consequence display developmental lethality on day 5 because of defects in brain formation, somatogenesis, and heart development (eg, tubular hearts and pericardial edema).26”
§ Macrophage development from HSCs requires PU.1-coordinated microRNA expression > Macrophage development requires microRNA expression
What the sources say
- Not checked — no full text of the sourcecites [26] Giraldez, 2005, MicroRNAs regulate brain morphogenesis in zebrafish., Science source
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.
It may state two separate claims as one.
In the paper
“whole-mount in situ hybridization against macrophage-specific L-plastin, which is strongly expressed from 18 hpf (the emergence of macrophages) on.44”
§ Macrophage development from HSCs requires PU.1-coordinated microRNA expression > Macrophage development requires microRNA expression
What the sources say
- Not checked — no full text of the sourcecites [44] Bennett, 2001, Myelopoiesis in the zebrafish, Danio rerio., Blood source
boosted- 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
“Although the molecular mechanism of this function is still unclear, it appears that miR-146a may control 2 transcriptional programs during myelopoiesis, one driving terminal differentiation along a selective myeloid path and another directing the specific migration of monocyte precursors into the peritoneum.”
§ Macrophage development from HSCs requires PU.1-coordinated microRNA expression > Discussion
hedgedconditional- 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.
It may state two separate claims as one.
In the paper
“Loss of expression of miR-146a, together with miR-145 loss, was implicated in the pathology of the 5qϪ myelodysplastic syndrome, 19 indicating its potential role as a tumor suppressor.”
§ Macrophage development from HSCs requires PU.1-coordinated microRNA expression > Discussion
What the sources say
- Not checked — no full text of the sourcecites [19] Starczynowski, 2010, Identification of miR-145 and miR-146a as mediators of the 5q- syndrome phenotype., Nat Med source
hedgedcorrelational- 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. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“HSCs in the zebrafish arise from the aortic endothelium 43 ;”
§ Macrophage development from HSCs requires PU.1-coordinated microRNA expression > Macrophage development requires microRNA expression
What the sources say
- Not checked yetcites [43] Bertrand, 2010, Haematopoietic stem cells derive directly from aortic endothelium during development., Nature source
Checked before — its earlier verdict is held back until a new check runs.
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.
- Not checked yet
None of the sources cited for this claim have been checked yet.
In the paper
“The combination of gain-and loss-of-function experiments in mice and zebrafish suggest that miR-146a plays an important role not only in inhibition of proinflammatory signaling or proliferation, 16,17,19 but also in directing an early, evolutionarily conserved differentiation program to promote the development of macrophages in both embryos and adults.”
§ Macrophage development from HSCs requires PU.1-coordinated microRNA expression > Discussion
What the sources say
- Not checked yetcites [16] Taganov, 2006, NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses., Proc Natl Acad Sci U S A source
- Not checked — no full text of the sourcecites [17] Starczynowski, 2011, MicroRNA-146a disrupts hematopoietic differentiation and survival., Exp Hematol source
- Not checked — no full text of the sourcecites [19] Starczynowski, 2010, Identification of miR-145 and miR-146a as mediators of the 5q- syndrome phenotype., Nat Med source
hedgeddirect- 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.
It may state two separate claims as one.
The paper relies on this without support.
Macrophage development in zebrafish begins at 18 hpf in the yolk sac and distributes macrophages during the first wave of primitive hematopoiesis through the blood circulation and migration into the mesenchyme of the head.
“macrophage development occurs from 18 hpf in the yolk sac and distributes macrophages during the first wave of primitive hematopoiesis through the blood circulation and migration into the mesenchyme of the head.”
The paper relies on this without support.
Supplementation of MZdicer KO embryos with mature miR-430 rescues early development without restoring macrophage development, so miR-430 does not itself promote macrophage emergence.
“Therefore, we examined macrophage development in the MZdicer ϩ430 mutants at 24-30 hpf by whole-mount in situ hybridization against macrophage-specific L-plastin”
The paper relies on this without support.
The antisense oligonucleotides used for miR-146a knockdown specifically reduce miR-146a activity without affecting other microRNAs or genes.
“Microinjection of 2 different antisense oligonucleotides (one targeting the stem loop and another the drosha cleavage region) into zebrafish eggs resulted in a massive reduction in L-plastin ϩ macrophage numbers (Figure 6B-C).”
The paper relies on this without support.
PU.1 binding to genomic regions indicates direct transcriptional regulation.
“Using global PU.1-binding data in combination with genomewide DNase HSS maps, we found that 4 of the PU.1 up-regulated miRs (miR-146a, miR-342, miR-338, and miR-155) harbored PU.1-binding peaks within open chromatin regions in their direct genomic vicinity.”
Citations
Cites
Heinz, S., Benner, C., Spann, N., Bertolino, E., Lin, Y. C., Laslo, P., Cheng, J. X., Murre, C., Singh, H., & Glass, C. K. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.05.004 · Cited by 13,382
Self-citationIn silico prediction of protein-protein interactions in human macrophages
Souiai, O., Guerfali, F. Z., Miled, S. B., Brun, C., & Benkahla, A. (2014) · BMC Research Notes · doi:10.1186/1756-0500-7-157 · Cited by 10,785
Significance analysis of microarrays applied to the ionizing radiation response
Tusher, V. G., Tibshirani, R., & Chu, G. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.091062498 · Cited by 10,568
Taganov, K. D., Boldin, M. P., Chang, K.-J., & Baltimore, D. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0605298103 · Cited by 4,317
Identification of tissue-specific microRNAs from mouse
Lagos-Quintana, M., Rauhut, R., Yalcin, A., Meyer, J., Lendeckel, W., & Tuschl, T. (2002) · Current Biology · doi:10.1016/s0960-9822(02)00809-6 · Cited by 3,355
MicroRNAs Modulate Hematopoietic Lineage Differentiation
Chen, C.-Z., Li, L., Lodish, H. F., & Bartel, D. P. (2004) · Science · doi:10.1126/science.1091903 · Cited by 3,257
Effective targeted gene ‘knockdown’ in zebrafish
Nasevicius, A., & Ekker, S. C. (2000) · Nature Genetics · doi:10.1038/79951 · Cited by 2,485
c-Myc-regulated microRNAs modulate E2F1 expression
O'Donnell, K. A., Wentzel, E. A., Zeller, K. I., Dang, C. V., & Mendell, J. T. (2005) · Nature · doi:10.1038/nature03677 · Cited by 2,347
Requirement of transcription factor PU.1 in the development of multiple hematopoietic lineages
Scott, E. W., Simon, M. C., Anastasi, J., & Singh, H. (1994) · Science · doi:10.1126/science.8079170 · Cited by 1,532
Tacke, F., Alvarez, D., Kaplan, T. J., Jakubzick, C., Spanbroek, R., Llodra, J., Garin, A., Liu, J., Mack, M., van Rooijen, N., et al. (2007) · Journal of Clinical Investigation · doi:10.1172/jci28549 · Cited by 1,323
Cited by
Sorted by citations
Menezes, S., Melandri, D., Anselmi, G., Perchet, T., Loschko, J., Dubrot, J., Patel, R., Gautier, E. L., Hugues, S., Longhi, M. P., et al. (2016) · Immunity · doi:10.1016/j.immuni.2016.12.001 · Cited by 288
The Kaleidoscope of Microglial Phenotypes
Dubbelaar, M. L., Kracht, L., Eggen, B. J. L., & Boddeke, E. W. G. M. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01753 · Cited by 260
Wei, Y., Nazari-Jahantigh, M., Chan, L., Zhu, M., Heyll, K., Corbalán-Campos, J., Hartmann, P., Thiemann, A., Weber, C., & Schober, A. (2013) · Circulation · doi:10.1161/circulationaha.112.000736 · Cited by 235
MicroRNAs, new effectors and regulators of NF‐κB
Boldin, M. P., & Baltimore, D. (2012) · Immunological Reviews · doi:10.1111/j.1600-065x.2011.01089.x · Cited by 199
Li, K., Ching, D., Luk, F. S., & Raffaı̈, R. L. (2015) · Circulation Research · doi:10.1161/circresaha.117.305844 · Cited by 211
Metadata
- Authors
- Ghani, S., Riemke, P., Schönheit, J., Lenze, D., Stumm, J., Hoogenkamp, M., Lagendijk, A., Heinz, S., Bonifer, C., Bakkers, J., Abdelilah-Seyfried, S., Hummel, M., & Rosenbauer, F.
- Affiliations
- Max Delbrück Center (DE)
- Charité – Universitätsmedizin Berlin (DE)
- University of Leeds (GB)
- Royal Netherlands Academy of Arts and Sciences (NL)
- University of California San Diego (US)
- Max-Delbrück-Center for Molecular Medicine, Berlin, Germany;
- ORCID
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2011-08-25
- Volume
- 118
- Issue
- 8
- Pages
- 2275-2284
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC10251560
- OpenAlex
- W1997338207
- Semantic Scholar
- bba41cf0cb9c3fbfc741609f6c4d1fe95d7ff8ab
- Cited by
- 123
- References
- 53
- Citations by year
- 2026: 6 · 2025: 3 · 2024: 4 · 2023: 5 · 2022: 7 · 2021: 3 · 2020: 6 · 2019: 9 · 2018: 8 · 2017: 6 · 2016: 10 · 2015: 5 · 2014: 11 · 2013: 28 · 2012: 11
- FWCI
- 10.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- KNAW Research Portal (The Royal Netherlands Academy of Arts and Sciences) (publishedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- KNAW research portal (Royal Academy of Art and Sciences (KNAW)) (submittedVersion, other-oa)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- PU.1, microRNA, hematopoietic stem cells, macrophage differentiation, myeloid differentiation, miR-146a, miR-155, miR-342, miR-338, Dicer, transcriptional regulation, peritoneal macrophages, zebrafish development, chromatin binding sites
- MeSH terms
- Proto-Oncogene Protein Spi-1, Animals, Cell Differentiation, Cell Line, Hematopoietic Stem Cells, Mice, Inbred C57BL, Proto-Oncogene Proteins, Zebrafish, Trans-Activators, Macrophages, Peritoneal, Cell Lineage, RNA, Small Interfering, MicroRNAs, Myelopoiesis, Mice, In Vitro Techniques
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 2026-11-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-11-10 (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.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
