The DOI matches its Crossref record; 59 of the 59 references it cites were found in a registry or an index; 43 of the 60 sources its claims cite were checked for support.
The emergent landscape of the mouse gut endoderm at single-cell resolution
Open accessAbstract
Here we delineate the ontogeny of the mammalian endoderm by generating 112,217 single-cell transcriptomes, which represent all endoderm populations within the mouse embryo until midgestation. We use graph-based approaches to model differentiating cells, which provides a spatio-temporal characterization of developmental trajectories and defines the transcriptional architecture that accompanies the emergence of the first (primitive or extra-embryonic) endodermal population and its sister pluripotent (embryonic) epiblast lineage. We uncover a relationship between descendants of these two lineages, in which epiblast cells differentiate into endoderm at two distinct time points-before and during gastrulation. Trajectories of endoderm cells were mapped as they acquired embryonic versus extra-embryonic fates and as they spatially converged within the nascent gut endoderm, which revealed these cells to be globally similar but retain aspects of their lineage history. We observed the regionalized identity of cells along the anterior-posterior axis of the emergent gut tube, which reflects their embryonic or extra-embryonic origin, and the coordinated patterning of these cells into organ-specific territories.
Overview
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Written from the paper’s full text.
TL;DR
This study generated 112,217 single-cell transcriptomes spanning mouse endoderm from E3.5 to E8.75 and used graph-based trajectory inference to map endoderm ontogeny. It shows that epiblast cells contribute to endoderm before and during gastrulation, that embryonic and extra-embryonic endoderm converge transcriptionally in the gut tube while retaining lineage memory, and that anterior-posterior organ territories are transcriptionally primed before overt organ formation.
Key findings
- Profiled 112,217 cells across 13 tissue types from E3.5 to E8.75, covering primitive/extra-embryonic endoderm, definitive/embryonic endoderm, and emergent gut endoderm.
- Identified an epiblast-to-endoderm contribution: a subset of EPI cells acquired endoderm identity before gastrulation, validated by Sox2-Cre lineage tracing (GFP-positive cells in emVE: 1–5 cells, 10/20 embryos) and tetraploid ESC chimeras (1–5 cells, 9/19 embryos); Ttr-Cre tracing showed no EPI contribution from VE (0/27 embryos).
- VE and DE descendants intermixed along the E8.75 gut tube AP axis, with DE enriched anteriorly and VE posteriorly; a classifier trained on E7.5 VE/DE cells achieved auROC 0.96 and predicted E8.75 origin with auROC 0.92, indicating retained lineage history.
- E8.75 gut tube cells ordered along AP pseudo-space matched the stereotypical order of organ identities; TF expression predicted AP pseudo-space with correlation 0.97, and a core set of 20 TFs was identified.
Methods
- Mouse embryos were collected from E3.5 to E8.75; pre-/early post-implantation stages used whole embryos, while E6.5–E8.75 used endodermal tissue enrichment, including Afp-GFP FACS to separate GFP-positive extra-embryonic and GFP-negative embryonic populations.
- Single-cell 3′ RNA-seq libraries were generated on the 10x Genomics Chromium platform, with 13 tissue types collected in duplicate or triplicate; bulk RNA-seq, in situ hybridization, immunofluorescence, and lineage tracing were used for validation.
- Computational analysis combined Harmony to bridge time-points with Palantir for pseudo-time, branch probabilities, and differentiation potential; Phenograph and tSNE were used for clustering/visualization, plus manifold classifiers and sparse regression models for AP pseudo-space and VE/DE classification.
Limitations
- The paper states that investigators were not blinded to allocation during experiments and outcome assessment.
- No formal limitations section is present; the text makes evident that findings are restricted to the mouse embryo and rely heavily on computational trajectory inference, with many predictions validated by imaging/ISH rather than functional perturbation.
- The study notes that Afp-GFP/Ttr-Cre-based discrimination of VE versus DE origin was limited to stages up to E8.75, the latest stage analyzed.
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Claims the paper makes
72 Own result · 32 Own interpretation · 19 Own method · 10 Supported · 9 Partly supported · 5 No full text of the sources · 2 Supported so far · 2 Couldn’t confirm · 2 Not checked yet · 2 No basis given · 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
“The changes in DP and BP suggest ICM lineage divergence into EPI and PrE occurs at E3.5 consistent with previous analyses using limited markers20,21”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Results > Emergence of primitive endoderm
What the sources say
- Supportedcites [20] Plusa, B., Piliszek, A., Frankenberg, S., Artus, J. & Hadjantonakis, A. K. Distinct sequential cell behaviours direct primitive endoderm formation in the mouse blastocyst. Development 135, 3081–3091 (2008). source
The Discussion (page unavailable) describes salt-and-pepper expression of EPI and PrE markers in the ICM of the E3.5 blastocyst. It also reports that EPI- and PrE-specific markers become mutually exclusive during the 32- to 64-cell transition, supporting lineage divergence at about this stage. (LLM, conf=0.90)
- Not checked — no full text of the sourcecites [21] Chazaud, C., Yamanaka, Y., Pawson, T. & Rossant, J. Early lineage segregation between epiblast and primitive endoderm in mouse blastocysts through the Grb2-MAPK pathway. Dev. Cell 10, 615–624 (2006). source
hedged- 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 authors state this as an assumption: Regions along pseudo-time where differentiation potential drops represent points where lineage specification and commitment occur.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Our previous studies revealed the gut endoderm to be comprised of cells of both PrE and DE (Extended Data Fig. 1a)5–7.”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Introduction
What the sources say
- Supportedcites [5] Viotti, M., Nowotschin, S. & Hadjantonakis, A. K. SOX17 links gut endoderm morphogenesis and germ layer segregation. Nat. Cell Biol. 16, 1146–1156 (2014). source
The Introduction states that the emergent mouse gut endoderm comprises cells of two origins, DE and VE. The Discussion describes these as embryonic and extraembryonic origins, supporting the citing sentence’s reference to DE and the PrE lineage. (LLM, conf=0.90)
- Supportedcites [6] Viotti, M., Nowotschin, S. & Hadjantonakis, A. K. Afp:mCherry, a red fluorescent transgenic reporter of the mouse visceral endoderm. Genesis 49, 124–133 (2011). source
In “Comparative reporter expression” (page not supplied), the paper describes epiblast-derived definitive endoderm cells intercalating among visceral endoderm cells and identifies visceral endoderm derivatives within the gut endoderm. The same section links visceral endoderm to the primitive endoderm lineage, supporting the claim that gut endoderm contains cells from both lineages. (LLM, conf=0.91)
- Supportedcites [7] Kwon, G. S., Viotti, M. & Hadjantonakis, A. K. The endoderm of the mouse embryo arises by dynamic widespread intercalation of embryonic and extraembryonic lineages. Dev. Cell 15, 509–520 (2008). source
The Results section, “Visceral endoderm-derived cells are incorporated into the gut tube” (page unavailable), reports visceral endoderm-derived cells in the gut-tube epithelium. The Introduction identifies definitive endoderm as the epiblast-derived lineage that forms the gut tube. Together, these passages support the claim of contributions from both lineages in the early mouse gut. (LLM, conf=0.90)
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.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“We also identified two PrE clusters at E3.5, which we propose represent nascent (light blue) and more advanced (dark blue) populations during lineage maturation22”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Results > Emergence of primitive endoderm
What the sources say
- Supportedcites [22] Artus, J., Piliszek, A. & Hadjantonakis, A. K. The primitive endoderm lineage of the mouse blastocyst: sequential transcription factor activation and regulation of differentiation by Sox17. Dev. Biol. 350, 393–404 (2011). source
The citing authors identify the two E3.5 clusters themselves; the citation supports their interpretation as stages of PrE maturation. The source’s Conclusions distinguish molecularly distinct sorted and unsorted PrE cells and propose sequential transcription-factor activation corresponding to successive periods of lineage development. (LLM, conf=0.88)
hedgedcorrelational- 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.
- The authors state this as an assumption: Regions along pseudo-time where differentiation potential drops represent points where lineage specification and commitment occur.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Based on the average diffusion distance10,11 from the bipotent inner cell mass (ICM), TE cells were substantially further away (13.9) from ICM than either EPI (0.41) or PrE (2.0) (Extended Data Fig. 4b, Methods)”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Results > Emergence of primitive endoderm
What the sources say
- Supportedcites [10] Setty, M. et al. Palantir characterizes cell fate continuities in human hematopoiesis. Preprint at https://www.biorxiv.org/content/early/2018/08/05/385328 (2018). source
The citation is attached to “diffusion distance,” identifying the measure used rather than sourcing the TE, EPI, and PrE values. The source’s “Measuring distances between cells using multi-scale distance” section defines diffusion distance between cells; the citing sentence points to its own Extended Data Fig. 4b and Methods for the numerical comparison. (LLM, conf=0.88)
- Supportedcites [11] Setty, M. et al. Characterization of cell fate probabilities in single-cell data with Palantir. Nat. Biotechnol. 37, 451–460 (2019). source
The citation is attached to the diffusion-distance method, not to the TE, EPI and PrE measurements. The paper’s “tSNE visualization” section describes scaling diffusion components to estimate diffusion distances; the numerical comparisons are the citing authors’ results. (LLM, conf=0.85)
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.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“These analyses provide precise ordering of markers during ICM lineage specification (Extended Data Fig. 5c)3,22,28.”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Results > Emergence of primitive endoderm
What the sources say
- Not checked — no full text of the sourcecites [3] Chazaud, C. & Yamanaka, Y. Lineage specification in the mouse preimplantation embryo. Development 143, 1063–1074 (2016). source
- Supportedcites [22] Artus, J., Piliszek, A. & Hadjantonakis, A. K. The primitive endoderm lineage of the mouse blastocyst: sequential transcription factor activation and regulation of differentiation by Sox17. Dev. Biol. 350, 393–404 (2011). source
In Results and discussion, the paper gives a specific sequence of marker activation—GATA6, PDGFRα, SOX17, GATA4, then SOX7—within the primitive endoderm lineage of the ICM. It describes this as a model supported by its observations, so the citation supports the ordering for that lineage. (LLM, conf=0.90)
- Partly supportedcites [28] Ohnishi, Y. et al. Cell-to-cell expression variability followed by signal reinforcement progressively segregates early mouse lineages. Nat. Cell Biol. 16, 27–37 (2014). sourceExperimental — accuracy not yet measured
The Results section (‘Progressive establishment of correlation’; page unavailable) reports an approximate activation hierarchy for seven PrE markers during the E3.5–E4.5 transition. It says evidence for a hierarchy was much weaker earlier, so it does not establish a precise ordering of markers throughout ICM lineage specification. (LLM, conf=0.86)
boostedcorrelational- 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.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Mouse mutants in both Fgfr1 and Fgfr2 phenocopy embryos lacking Fgf4, with defects in PrE specification and exit from naïve pluripotency in the EPI26,27,29.”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Results > Emergence of primitive endoderm
What the sources say
- Partly supportedcites [26] Molotkov, A., Mazot, P., Brewer, J. R., Cinalli, R. M. & Soriano, P. Distinct requirements for FGFR1 and FGFR2 in primitive endoderm development and exit from pluripotency. Dev. Cell 41, 511–526 (2017). sourceExperimental — accuracy not yet measured
The Results (page unavailable) say Fgfr1/Fgfr2 double-null embryos phenocopy Fgf4-null embryos in disrupted PrE development. The Discussion (page unavailable) says PrE cells appear to be specified but not maintained, contrary to the claim of defective specification. It also reports persistent Nanog in mutant embryos and proposes impaired EPI maturation, while the direct exit-from-pluripotency experiments used ES cells. (LLM, conf=0.88)
- Supportedcites [27] Kang, M., Garg, V. & Hadjantonakis, A. K. Lineage establishment and progression within the inner cell mass of the mouse blastocyst requires FGFR1 and FGFR2. Dev. Cell 41, 496–510 (2017). source
The Discussion (page not provided) explicitly says Fgfr1/Fgfr2 double mutants fail to specify PrE and phenocopy Fgf4 mutants. The Results (page not provided) report that their EPI cells fail to downregulate NANOG and do not progress in lineage maturation; the Discussion interprets this failure as remaining in a naïve pluripotent state. (LLM, conf=0.94)
- Not checked — no full text of the sourcecites [29] Kang, M., Piliszek, A., Artus, J. & Hadjantonakis, A. K. FGF4 is required for lineage restriction and salt-and-pepper distribution of primitive endoderm factors but not their initial expression in the mouse. Development 140, 267–279 (2013). 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.
- Partly supported
None of the sources cited for this claim have been checked yet.
In the paper
“Common endodermal genes are expressed by both cell types hampering marker-based discrimination of embryonic and extra-embryonic descendants8,9.”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Introduction
What the sources say
- Could not verifycites [8] Sherwood, R. I., Chen, T. Y. & Melton, D. A. Transcriptional dynamics of endodermal organ formation. Dev. Dyn. 238, 29–42 (2009). sourceExperimental — accuracy not yet measured
The Results section on microarray analysis describes markers shared across or restricted to embryonic endodermal organ populations, but does not compare primitive endoderm (PrE) with definitive endoderm (DE). Searches for primitive endoderm, extraembryonic endoderm, and shared markers found no passage addressing whether common genes hamper discrimination between those lineages. No page number is available in our copy. (LLM, conf=0.76)
- Not checked yetcites [9] Hou, J. et al. A systematic screen for genes expressed in definitive endoderm by Serial Analysis of Gene Expression (SAGE). BMC Dev. Biol. 7, 92 (2007).
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.
- Could not verify
Every source the paper cites for this claim was checked and supports it.
In the paper
“At gastrulation (E7.0-E7.5), EPI-derived (embryonic) DE cells intercalate into the emVE epithelium to form the gut endoderm5,7.”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > DISCUSSION
What the sources say
- Supportedcites [5] Viotti, M., Nowotschin, S. & Hadjantonakis, A. K. SOX17 links gut endoderm morphogenesis and germ layer segregation. Nat. Cell Biol. 16, 1146–1156 (2014). source
The Introduction says that epiblast-derived DE cells insert into the emVE epithelium and that the resulting mixed population forms the gut endoderm. The Results describe the process at E7.0, E7.25 and E7.5, when the embryo’s surface contains both emVE descendants and epiblast-derived DE cells. (LLM, conf=0.94)
- Supportedcites [7] Kwon, G. S., Viotti, M. & Hadjantonakis, A. K. The endoderm of the mouse embryo arises by dynamic widespread intercalation of embryonic and extraembryonic lineages. Dev. Cell 15, 509–520 (2008). source
The Results section places definitive-endoderm emergence at E7.0–E7.5. The Discussion states that epiblast-derived cells intercalate into the pre-existing visceral endoderm epithelium; the paper also describes the resulting mixed lineage and its contribution to the gut tube. (LLM, conf=0.90)
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.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Gut endoderm comprises EPI-derived DE and VE descendants6,7.”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Results > Anterior-Posterior patterning of gut endoderm
What the sources say
- Supportedcites [6] Viotti, M., Nowotschin, S. & Hadjantonakis, A. K. Afp:mCherry, a red fluorescent transgenic reporter of the mouse visceral endoderm. Genesis 49, 124–133 (2011). source
The Comparative reporter expression section describes epiblast-derived definitive endoderm cells intercalating among visceral endoderm cells and reports that visceral endoderm derivatives are incorporated into the gut tube. Together, these passages support both lineages contributing to gut endoderm; page numbers are not provided in our copy. (LLM, conf=0.92)
- Supportedcites [7] Kwon, G. S., Viotti, M. & Hadjantonakis, A. K. The endoderm of the mouse embryo arises by dynamic widespread intercalation of embryonic and extraembryonic lineages. Dev. Cell 15, 509–520 (2008). source
The Results (‘Visceral endoderm-derived cells are incorporated into the gut tube’) report VE-derived cells in the gut-tube epithelium alongside cells of epiblast origin. The Discussion identifies the intercalating epiblast-derived cells as definitive endoderm and describes the embryonic gut tube as having a dual origin. (LLM, conf=0.93)
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.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“13ss (E8.75), approximately corresponding to midgestation, the latest stage analyzed in this study, is the latest stage for unambiguous assignment of visceral endoderm (VE)-vs.-definitive endoderm (DE) origin of gut tube cells using Afp-GFP7,12 or Ttr-Cre7,35 mouse lines.”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Methods > Dissociation of embryos and collection of single cells
What the sources say
- Partly supportedcites [7] Kwon, G. S., Viotti, M. & Hadjantonakis, A. K. The endoderm of the mouse embryo arises by dynamic widespread intercalation of embryonic and extraembryonic lineages. Dev. Cell 15, 509–520 (2008). sourceExperimental — accuracy not yet measured
The Results section, “Visceral endoderm-derived cells are incorporated into the gut tube” (page unavailable), supports using Afp::GFP and Ttr::Cre to identify visceral endoderm-derived gut cells and says reporter reactivation precluded analysis at 20+ somites. It reports analysis at 12–18 somites, however, so it does not support 13 somites as the latest stage for unambiguous assignment. (LLM, conf=0.88)
- Partly supportedcites [12] Kwon, G. S. et al. Tg(Afp-GFP) expression marks primitive and definitive endoderm lineages during mouse development. Dev. Dyn. 235, 2549–2558 (2006). sourceExperimental — accuracy not yet measured
The Introduction (page not provided) identifies Afp-GFP mouse lines as tools for tagging and tracking primitive and definitive endodermal cells. It does not establish that 13ss (E8.75) is the latest stage for unambiguous assignment of gut-tube cell origin, and the cited passages do not address Ttr-Cre. (LLM, conf=0.86)
- Partly supportedcites [35] Kwon, G. S. & Hadjantonakis, A. K. Transthyretin mouse transgenes direct RFP expression or Cre-mediated recombination throughout the visceral endoderm. Genesis 47, 447–455 (2009). sourceExperimental — accuracy not yet measured
The ‘ADDITIONAL SITES OF RFP EXPRESSION AND Cre RECOMBINATION IN LATE STAGE EMBRYOS’ section says later transgene activity precludes further analysis of visceral-endoderm-derived cells in embryonic endoderm derivatives. It does not establish that 13 somites (E8.75) is the latest stage at which gut-tube cell origins can be unambiguously assigned using Afp-GFP or Ttr-Cre. Page numbers are unavailable in our copy. (LLM, conf=0.84)
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.
- Partly supported
- Probably not a substantial claim. 25
- It may state two separate claims as one. 47
- The quote only partly states this claim. 1
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Later, around E7.0, definitive (embryonic) endoderm (DE) is specified from pluripotent epiblast (EPI) at gastrulation4.”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Introduction
What the sources say
- Partly supportedcites [4] Nowotschin, S. & Hadjantonakis, A. K. Cellular dynamics in the early mouse embryo: from axis formation to gastrulation. Curr. Opin. Genet. Dev. 20, 420–427 (2010). sourceExperimental — accuracy not yet measured
The ‘Emergence of the primitive streak’ section says that during gastrulation the epiblast generates definitive endoderm, and ‘Intercalation and endoderm morphogenesis’ says DE cells may be specified within the streak. The paper places streak formation at E6.5 and its elongation through E7.5, but does not specifically place DE specification around E7.0. (LLM, conf=0.82)
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.
- Partly supported
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
“The gut endoderm is the precursor of the respiratory and digestive tracts, and their associated organs1,2 (Fig. 1).”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Introduction
What the sources say
- Supportedcites [1] Zorn, A. M. & Wells, J. M. Vertebrate endoderm development and organ formation. Annu. Rev. Cell Dev. Biol. 25, 221–251 (2009). source
The Introduction states that definitive endoderm gives rise to cells lining the respiratory and digestive systems and contributes to their associated organs. It also describes the gut tube developing into the trachea, lungs, gastrointestinal tract, and other organs, supporting the paraphrase. (LLM, conf=0.94)
- Not checked — no full text of the sourcecites [2] Tremblay, K. D. Formation of the murine endoderm: lessons from the mouse, frog, fish, and chick. Prog. Mol. Biol. Transl. Sci. 96, 1–34 (2010). 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.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“ICM cell fate specification is driven in part by the lineage-specific transcription factors (TFs) Gata6 and Nanog, which are co-expressed in uncommitted ICM, and exclusively expressed in, and required for, PrE and EPI respectively23,24.”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Results > Emergence of primitive endoderm
What the sources say
- Partly supportedcites [23] Silva, J. et al. Nanog is the gateway to the pluripotent ground state. Cell 138, 722–737 (2009). sourceExperimental — accuracy not yet measured
The Results section on Nanog localization (page not provided) identifies Gata6 as a hypoblast specification factor and reports that Gata6 and Nanog occupy mutually exclusive cells by E4.5. The Discussion (page not provided) says Nanog is exclusively expressed in nascent epiblast and is essential for its transition to pluripotency. Our copy does not establish that Gata6 and Nanog are co-expressed in uncommitted ICM cells or that Gata6 is required for primitive endoderm formation. (LLM, conf=0.88)
- Partly supportedcites [24] Schrode, N., Saiz, N., Di Talia, S. & Hadjantonakis, A. K. GATA6 levels modulate primitive endoderm cell fate choice and timing in the mouse blastocyst. Dev. Cell 29, 454–467 (2014). sourceExperimental — accuracy not yet measured
The Introduction and Results describe GATA6 and NANOG as lineage-specific transcription factors that are initially co-expressed in ICM cells and later become mutually exclusive in PrE and EPI precursors. The Results establish that GATA6 is required for PrE specification. Our copy identifies NANOG with EPI but does not establish that NANOG is required for EPI specification. (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.
Probably not a substantial claim. 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
“The early post-implantation (E5.5, Fig. 1) mouse embryo is radially symmetrical, and the VE appears morphologically uniform around its proximal-distal axis4,33.”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Results > Embryonic and extraembryonic visceral endoderm
What the sources say
- Partly supportedcites [4] Nowotschin, S. & Hadjantonakis, A. K. Cellular dynamics in the early mouse embryo: from axis formation to gastrulation. Curr. Opin. Genet. Dev. 20, 420–427 (2010). sourceExperimental — accuracy not yet measured
The section “PD polarity at early postimplantation results in DVE cell specification” describes the E5.5 egg cylinder as radially symmetric. It does not establish that the VE appears morphologically uniform around the proximal-distal axis; instead, it describes distinct proximal and distal VE morphologies and morphologically distinct DVE cells around E5.5. The source therefore supports the embryo-symmetry part but not the unqualified VE-uniformity part. (LLM, conf=0.84)
- Not checked — no full text of the sourcecites [33] Arnold, S. J. & Robertson, E. J. Making a commitment: cell lineage allocation and axis patterning in the early mouse embryo. Nat. Rev. Mol. Cell Biol. 10, 91–103 (2009). source
hedged- 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.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“While active across the ICM population25–27, FGF4 signaling is critical for PrE specification28,29.”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Results > Emergence of primitive endoderm
What the sources say
- Supportedcites [25] Morgani, S. M. et al. A Sprouty4 reporter to monitor FGF/ERK signaling activity in ESCs and mice. Dev. Biol. 441, 104–126 (2018). source
The Results section reports Spry4 expression in all ICM cells from E3.5 and states that absence of Fgf4 prevents PrE formation. The Discussion concludes that all ICM cells appear to transduce the FGF4 signal, although signaling levels vary between cells. (LLM, conf=0.90)
- Partly supportedcites [26] Molotkov, A., Mazot, P., Brewer, J. R., Cinalli, R. M. & Soriano, P. Distinct requirements for FGFR1 and FGFR2 in primitive endoderm development and exit from pluripotency. Dev. Cell 41, 511–526 (2017). sourceExperimental — accuracy not yet measured
The citation is attached to the claim that FGF4 signaling is critical for PrE specification, not to the preceding claim about activity across the ICM. The Discussion says FGF4 promotes conversion of ICM cells toward a PrE fate. However, the Results section “Fgfr1 and Fgfr2 are Required for Maintenance but not Initiation of the PrE” says PrE development begins without FGF signaling but is not maintained, so the claim overstates its role in initial specification. Page numbers were not available in our copy. (LLM, conf=0.87)
- Supportedcites [27] Kang, M., Garg, V. & Hadjantonakis, A. K. Lineage establishment and progression within the inner cell mass of the mouse blastocyst requires FGFR1 and FGFR2. Dev. Cell 41, 496–510 (2017). source
The Results section states that FGFR1 is required to relay the FGF4 signal to establish a PrE fate in ICM cells. The Discussion also reports complete failure of PrE specification when both FGFR1 and FGFR2 are absent. The citation to this paper attaches to the PrE-specification clause, not the preceding claim about activity across the ICM. (LLM, conf=0.94)
- Supportedcites [28] Ohnishi, Y. et al. Cell-to-cell expression variability followed by signal reinforcement progressively segregates early mouse lineages. Nat. Cell Biol. 16, 27–37 (2014). source
The Results section (“Fgf4 is required for EPI versus PrE segregation,” Fig. 6) reports that loss of Fgf4 arrests PrE differentiation and significantly suppresses PrE-specific markers. The Discussion also describes an absence of PrE cells in embryos lacking Fgf4. The separate claim that signaling is active across the ICM is attached to other citations, not this one. (LLM, conf=0.93)
- Not checked — no full text of the sourcecites [29] Kang, M., Piliszek, A., Artus, J. & Hadjantonakis, A. K. FGF4 is required for lineage restriction and salt-and-pepper distribution of primitive endoderm factors but not their initial expression in the mouse. Development 140, 267–279 (2013). source
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.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Differential expression between bulk RNA sequenced E7.5 exVE and emVE populations suggested that emVE represents a specialized variant of exVE (Extended Data Fig. 7d), perhaps modulating a transcriptional program in response to stimuli, such as BMP or Nodal38–40.”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Results > Embryonic and extraembryonic visceral endoderm
What the sources say
- Supportedcites [38] Paca, A. et al. BMP signaling induces visceral endoderm differentiation of XEN cells and parietal endoderm. Dev. Biol. 361, 90–102 (2012). source
The citing authors attribute their RNA-sequencing interpretation to their own data; this citation supports BMP as an example of a stimulus that may shape VE differences. In the Discussion, the source proposes that BMP signaling promotes phenotypic differences between exVE and emVE and drives differentiation toward an exVE fate. It does not need to establish the citing authors’ separate claim about emVE being a specialized variant. (LLM, conf=0.88)
- Supportedcites [39] Kruithof-de Julio, M. et al. Regulation of extra-embryonic endoderm stem cell differentiation by Nodal and Cripto signaling. Development 138, 3885–3895 (2011). source
The citation supports the Nodal example in the sentence, rather than the citing authors’ E7.5 RNA-sequencing inference. The Introduction says Nodal is required for EmVE differentiation and describes its signaling-mediated transcriptional responses; “Gene expression changes during XEN cell differentiation” reports altered gene expression after Nodal treatment. This paper does not establish BMP’s role or the E7.5 comparison, but those are not specifically attributed to this source. (LLM, conf=0.86)
- Partly supportedcites [40] Artus, J. et al. BMP4 signaling directs primitive endoderm-derived XEN cells to an extraembryonic visceral endoderm identity. Dev. Biol. 361, 245–262 (2012). sourceExperimental — accuracy not yet measured
In Results and Discussion (page unavailable), the paper reports that BMP4 changes gene expression in XEN cells toward an exVE-like identity, supporting BMP as a stimulus that can modulate a visceral-endoderm program. It does not show that emVE is a specialized variant of exVE or that emVE modulates its program in response to BMP. The Introduction mentions Nodal-induced XEN-cell differentiation, but does not establish a Nodal response in emVE. (LLM, conf=0.83)
hedgedconditional- 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.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Proximal-distal spatial patterning across the VE has been described preceding, and coincident to the onset of gastrulation at E6.5, with a clear distinction between the morphology and function of the proximally located exVE (cuboidal epithelium, overlying the ExE, giving rise to yolk sac endoderm, YsE) and distal emVE (squamous epithelium, overlying the epiblast, contributing to the gut tube7).”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Results > Embryonic and extraembryonic visceral endoderm
What the sources say
- Supportedcites [7] Kwon, G. S., Viotti, M. & Hadjantonakis, A. K. The endoderm of the mouse embryo arises by dynamic widespread intercalation of embryonic and extraembryonic lineages. Dev. Cell 15, 509–520 (2008). source
The citation is attached to the claim that distal embryonic visceral endoderm contributes to the gut tube. In Results, “Visceral endoderm-derived cells are incorporated into the gut tube” (page unavailable), the authors report that cells originating in visceral endoderm positioned distally over the epiblast were eventually incorporated into the gut-tube epithelium. (LLM, conf=0.93)
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.
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
“Cell fate is determined through a combination of cell intrinsic propensities to specific fates and extrinsic cues (e.g. signaling) from the environment, detailed knowledge of which should yield improved protocols for differentiation into distinct endodermal derivatives49.”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > DISCUSSION
What the sources say
- Partly supportedcites [49] McCauley, H. A. & Wells, J. M. Pluripotent stem cell-derived organoids: using principles of developmental biology to grow human tissues in a dish. Development 144, 958–962 (2017). sourceExperimental — accuracy not yet measured
The Introduction explains that external signals, including Wnt and FGF, direct PSC-derived endoderm toward distinct fates, supporting the role of extrinsic cues and their use in differentiation protocols. It does not establish the claimed contribution of cell-intrinsic propensities to fate determination. (LLM, conf=0.83)
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.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“TF expression was exceptionally accurate in predicting AP pseudo-space order (Extended Data Fig. 9c, Correlation: 0.97), indicating that transcriptional regulation, presumably in response to signals from neighboring mesenchyme1, plays a key role in gut tube patterning.”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Results > Emergence of organ identities
What the sources say
- Supportedcites [1] Zorn, A. M. & Wells, J. M. Vertebrate endoderm development and organ formation. Annu. Rev. Cell Dev. Biol. 25, 221–251 (2009). source
Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
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.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“The high resolution achieved by Palantir allows detailed mapping of gene expression trends and dynamics that are correlated with changes in lineage potential10,11.”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Methods > Palantir
What the sources say
- Supportedcites [10] Setty, M. et al. Palantir characterizes cell fate continuities in human hematopoiesis. Preprint at https://www.biorxiv.org/content/early/2018/08/05/385328 (2018). source
In “The Palantir Algorithm” (page not supplied), the paper says Palantir enables precise comparison of gene-expression dynamics across lineages. In the passage labeled “Slingshot” (page not supplied), it links its high-resolution mapping to lineage choices and explicitly associates expression changes with changes in lineage commitment. (LLM, conf=0.94)
- Supportedcites [11] Setty, M. et al. Characterization of cell fate probabilities in single-cell data with Palantir. Nat. Biotechnol. 37, 451–460 (2019). source
The Results (The Palantir Algorithm) say Palantir’s pseudotime enables precise characterization of gene expression dynamics across lineages. The Results (Comparison with trajectory inference algorithms) explicitly say it associates expression changes in key transcription factors with changes in lineage commitment. No page numbers are provided in our copy. (LLM, conf=0.93)
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.
Probably not a substantial claim.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“A key distinguishing feature of Palantir is that rather than treating lineage decisions as bifurcations, cell fate choices are modeled as continuous probabilistic processes.”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Methods > Palantir
What the sources say
- Supportedcites [10] Setty, M. et al. Palantir characterizes cell fate continuities in human hematopoiesis. Preprint at https://www.biorxiv.org/content/early/2018/08/05/385328 (2018). source
The Comparison of Palantir to other pseudotime algorithms section explicitly describes Palantir as using a continuous, probabilistic model of cell fate potential, in contrast to algorithms that model differentiation as discrete, deterministic bifurcations. The Introduction likewise says Palantir models continuity in both cell state and fate choice. (LLM, conf=0.95)
- Supportedcites [11] Setty, M. et al. Characterization of cell fate probabilities in single-cell data with Palantir. Nat. Biotechnol. 37, 451–460 (2019). source
The Discussion explicitly says Palantir models cell fate choice as a continuous probabilistic process. It also contrasts Palantir with algorithms that treat lineage choices as discrete bifurcations. (LLM, conf=0.95)
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.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Palantir results however have been shown to be robust to these parameters10,11,”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Methods > Palantir
What the sources say
- Supportedcites [10] Setty, M. et al. Palantir characterizes cell fate continuities in human hematopoiesis. Preprint at https://www.biorxiv.org/content/early/2018/08/05/385328 (2018). source
The section on application to hematopoiesis says Palantir’s pseudo-time and differentiation potential were robust across a wide range of input parameters. The robustness discussion also reports that results were very robust across the tested settings for graph neighbors, diffusion components, and waypoint samples. (LLM, conf=0.94)
- Supportedcites [11] Setty, M. et al. Characterization of cell fate probabilities in single-cell data with Palantir. Nat. Biotechnol. 37, 451–460 (2019). source
The Results section reports that Palantir’s pseudo-time and differentiation potential were robust across a wide range of parameter choices. The ‘Application of Palantir to CD34+ cells’ section also states that results were stable to the choice of k, number of diffusion components, and waypoints. (LLM, conf=0.94)
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.
- Supported
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“Right: Plot generated using mnnCorrect27 for global batch effect correction leading to “over-correction” and loss in signal between time-points.”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Extended Data
What the sources say
- Could not verifycites [27] Kang, M., Garg, V. & Hadjantonakis, A. K. Lineage establishment and progression within the inner cell mass of the mouse blastocyst requires FGFR1 and FGFR2. Dev. Cell 41, 496–510 (2017). sourceExperimental — accuracy not yet measured
The STAR METHODS sections describe fluorescence-decay correction and normalization of single-cell gene-expression data, but do not discuss mnnCorrect or global batch-effect correction. The Results report that E3.5 and E4.5 cells generally clustered apart, but do not assess over-correction or loss of signal between time-points. Searches for mnnCorrect and batch correction found no passage addressing the claim. (LLM, conf=0.76)
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.
- 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
“Trajectories of endoderm cells were mapped as they acquired embryonic versus extra-embryonic fates, and as they spatially converged within the nascent gut endoderm; revealing them to be globally similar but retaining aspects of their lineage history.”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Abstract
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
“Gata6/Fgf4 also tracked with EPI specification, but trailed Gata6/Nanog.”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Results > Emergence of primitive endoderm
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
“At E5.5, GFP-positive Gata6-positive cells were observed in distal locations, whereas by E6.0, they predominantly resided more anteriorly (Extended Data Fig. 6f).”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Results > Differentiation of epiblast to endoderm
plaincorrelational- 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
“Additional genes correlated along pseudo-time with Fgf4 in EPI (e.g. Tcf7l1, Extended Data Fig. 5d, b, e–f, green arrowhead), and Gata6 and Gata4 in PrE (Extended Data Fig. 5b, Supplementary Fig. 3).”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Results > Emergence of primitive endoderm
plaincorrelational- 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
“The Gata6/Nanog ratio closely tracked with EPI specification and a strong descriptor of ICM fate specification (Extended Data Fig. 5b).”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Results > Emergence of primitive endoderm
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 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 the regionalized identity of cells along the anterior-posterior axis of the emergent gut tube, reflecting their embryonic or extra-embryonic origin, and their coordinate patterning into organ-specific territories.”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Abstract
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
“Palantir ordered cells along their developmental trajectories with high DP at E3.5, corresponding to EPI-vs.-PrE lineage divergence (Fig. 2b).”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Results > Differentiation of epiblast to endoderm
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.
- The authors state this as an assumption: Regions along pseudo-time where differentiation potential drops represent points where lineage specification and commitment occur.
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
“Imaging of E5.5-E6.0 Sox2-CreTG/+;ROSA26mTmG/+ embryos revealed the majority of GFP-positive cells within the EPI, with single cells also observed within the emVE (yellow arrowhead, 1–5 cells, 10/20 embryos), but not extra-embryonic (ex)VE.”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Results > Differentiation of epiblast to endoderm
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
“Palantir suggested Fgfr1 was expressed in uncommitted ICM cells (Extended Data Fig. 5a, c–d), and downregulated upon PrE specification, at the time of transient Fgfr2 activation.”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Results > Emergence of primitive endoderm
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.
Probably not a substantial claim. 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
“By contrast, all GFP-positive cells were restricted to the VE in Ttr-CreTG/+;ROSA26mTmG embryos, with no cells detected in the EPI (0/27 embryos, Fig. 2e, Extended Data Fig. 6f).”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Results > Differentiation of epiblast to endoderm
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
“Two ICM clusters were identified; one representing uncommitted cells having equal propensity for PrE or EPI fates (purple), and another (green), that albeit uncommitted, had started to specify towards PrE or EPI”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Results > Emergence of primitive endoderm
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 authors state this as an assumption: Regions along pseudo-time where differentiation potential drops represent points where lineage specification and commitment occur.
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 data also define previously unappreciated sub-states within well-studied cell populations and uncovered detailed gene expression trends.”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > 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.
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
“While not all Hox genes were expressed within the E8.75 gut tube, of those that were, the majority were posteriorly localized (Fig. 5d and Extended Data Fig. 10), including several displaying robust, more anterior expression within mesoderm and/or neurectoderm (Extended Data Fig. 10: Hoxb1, Hoxd4).”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Results > Emergence of organ identities
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
“We observed a high degree of variability in the density of cells along the pseudo-spatial axis (Fig. 5b–c, Extended Data Fig. 9a–b), with low density regions between clusters.”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Results > Emergence of organ identities
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.
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
“By the time the gut endoderm has internalized forming the gut tube (E8.75), clusters of cells expressing markers of organ identity could be identified, correlating in AP pseudo-space with the stereotypical order of endodermal organs.”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > DISCUSSION
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
“BMP, HH, JAK/STAT and HIPPO pathway activation encompassed multiple domains, Nodal signaling was not active at this stage, while both positive and negative read-outs of Retinoic Acid signaling were posteriorly localized.”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Results > Emergence of organ identities
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 genes were expressed at substantial levels in both VE and DE cells, and at comparable AP positions, except for Nkx2–1, which is expressed in the anterior-most cells of the gut tube and therefore exclusive to DE (Fig. 4c).”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Results > Anterior-Posterior patterning of gut endoderm
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
“Based on the expression of marker genes in scRNA-seq data, and correlation to bulk RNA-seq gene expression of sorted E7.5 exVE and emVE tissues, cells specifying towards YsE and gut tube were exVE and emVE, respectively, consistent with reported spatial patterning at these stages (Extended Data Fig. 7c–e).”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Results > Embryonic and extraembryonic visceral endoderm
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 claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“emVE-specific genes (Fig. 3c, Cluster 1) included Lhx1 and Lefty1, and AVE-specific genes Cer1 and Hhex30,32,37. ExVE-specific genes (Fig. 3c, Cluster 2) included Apln and Msx1 (Supplementary Table 4).”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Results > Embryonic and extraembryonic visceral endoderm
What the sources say
- Not checked — no full text of the sourcecites [30] Thomas, P. Q., Brown, A. & Beddington, R. S. Hex: a homeobox gene revealing peri-implantation asymmetry in the mouse embryo and an early transient marker of endothelial cell precursors. Development 125, 85–94 (1998). source
- Not checked — no full text of the sourcecites [32] Belo, J. A. et al. Cerberus-like is a secreted factor with neutralizing activity expressed in the anterior primitive endoderm of the mouse gastrula. Mech. Dev. 68, 45–57 (1997). source
- Not checked — no full text of the sourcecites [37] Takaoka, K., Yamamoto, M. & Hamada, H. Origin and role of distal visceral endoderm, a group of cells that determines anterior–posterior polarity of the mouse embryo. Nat. Cell Biol. 13, 743–752 (2011). source
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
“Our data validate FGF and WNT, and reveal NOTCH signaling at the posterior (small/large intestine clusters, Fig. 5).”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Results > Emergence of organ identities
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
“To explore this further, we identified two covarying gene sets (Supplementary Fig. 5b) exhibiting contrasting expression patterns in putative E5.5 exVE and emVE cells (Fig. 3c), and also distinguished bona fide exVE and emVE cells at E6.5 and E7.5 (Extended Data Fig. 7g).”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Results > Embryonic and extraembryonic visceral endoderm
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
“Consistent with previous findings, there was extensive intermixing of these descendants along the AP pseudo-space axis with enrichment of DE descendants in the anterior, and VE descendants in the posterior (Fig. 4b).”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Results > Anterior-Posterior patterning of gut endoderm
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In the paper
“Interestingly, VE cells at E5.5 were distributed across pseudo-time (Extended Data Fig. 7a): a subset did not exhibit any change in DP indicating a more uncommitted state (Extended Data Figs. 7e–f), while the majority exhibited altered DP indicating propensity towards YsE-vs.-gut tube (Extended Data Figs. 7e–f).”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Results > Embryonic and extraembryonic visceral endoderm
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- The authors state this as an assumption: Regions along pseudo-time where differentiation potential drops represent points where lineage specification and commitment occur.
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
“Yellow arrowheads point cells of epiblast (EPI) origin present within the visceral endoderm (VE) epithelial layer.”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Extended Data
plainn = 10- Asserted: passes — The authors put it forward as true.
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In the paper
“Black and orange arrowheads mark presumptive ParE and VE lineages, respectively.”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Extended Data
plaincorrelational- 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.
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In the paper
“Gene expression patterns of Tcf7l1 and Nanog depicting similar expression of Tcf7l1 in EPI as Fgf4 (green arrowhead).”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Extended Data
plaincorrelationaln = 14- 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.
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In the paper
“The average distance between pairs of ICM and TE cells (13.9) at E3.5 and is orders of magnitude greater than distance between pairs of ICM and EPI (0.41) or PrE (2.0) cells (Fig. 2b).”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Methods > Trophectoderm lineage decision (Related to Fig. 2)
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In the paper
“In contrast, the path from EPI to VE boundary cells includes relatively uniform step sizes and does not include substantially large steps indicating continuity (Extended Data Fig. 6d).”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Methods > Relationship between EPI, VE and ExE cells at E5.5
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In the paper
“Primitive (extra-embryonic) endoderm (PrE) cells arise at the blastocyst stage, around mouse embryonic (E) day 3.5–4.03, and predominantly contribute to parietal and visceral yolk sac endoderm.”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Introduction
What the sources say
- Not checked — no full text of the sourcecites [3] Chazaud, C. & Yamanaka, Y. Lineage specification in the mouse preimplantation embryo. Development 143, 1063–1074 (2016). source
plaindirect- Asserted: passes — The authors put it forward as true.
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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
“Trans-migrating cells were Gata6-positive, indicating they had acquired an endoderm identity.”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Results > Differentiation of epiblast to endoderm
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“By E4.5, when Fgfr1 and Fgfr2 are no longer expressed, a second phase of FGF signaling in PrE could be mediated by Fgf5/Fgf8-Fgfr4 in emergent VE and Fgf3-Fgfr3 in ParE (Extended Data Fig. 5d, orange and black arrowheads).”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Results > Emergence of primitive endoderm
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.
In the paper
“Symmetry is broken, and the AP axis established through the migration of AVE37.”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Results > Embryonic and extraembryonic visceral endoderm
What the sources say
- Not checked — no full text of the sourcecites [37] Takaoka, K., Yamamoto, M. & Hamada, H. Origin and role of distal visceral endoderm, a group of cells that determines anterior–posterior polarity of the mouse embryo. Nat. Cell Biol. 13, 743–752 (2011). source
plaindirect- Asserted: passes — The authors put it forward as true.
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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
“Comparison to bulk RNA-seq data demonstrated that isolation and dissociation did not alter cell proportions or transcriptional profiles (Extended Data Figs. 1c, 2b).”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Results
boosted- Asserted: passes — The authors put it forward as true.
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In the paper
“Cluster-specific expression was validated using ISH, confirming the accuracy of inferred AP pseudo-space, and the emergence of endodermal organ identities at E8.75 (Extended Data Fig. 9a).”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Results > Emergence of organ identities
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The inferred pseudo-space was robust to different parameters and reproducible across replicates (Extended Data Fig. 8e–g).”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Results > Anterior-Posterior patterning of gut endoderm
plain- Asserted: passes — The authors put it forward as true.
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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
“While cells develop a marked propensity towards specific cell fates earlier than previously appreciated, they nevertheless retain a remarkable degree of plasticity.”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > DISCUSSION
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- The authors state this as an assumption: Regions along pseudo-time where differentiation potential drops represent points where lineage specification and commitment occur.
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 corroborate AP ordering reflecting spatial distribution along the gut tube, we confirmed consistency between gene expression trends from scRNA-seq data with bulk RNA-seq data of micro-dissected gut tube quadrants, such that Nkx2–1 an anterior gene, and Hoxb9, a posterior gene, exhibited consistent expression patterns (Extended Data Fig. 8c).”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Results > Anterior-Posterior patterning of gut endoderm
plaincorrelational- Asserted: passes — The authors put it forward as true.
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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
“All samples were generated in duplicate.”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Methods > Bulk RNA-seq processing
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 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
“Taken together, these data reveal that at the transcriptional level, spatial patterning exists at E5.5, preceding morphological changes within the VE.”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Results > Embryonic and extraembryonic visceral endoderm
plaincorrelational- 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.
- The authors state this as an assumption: Regions along pseudo-time where differentiation potential drops represent points where lineage specification and commitment occur.
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 data suggest that gut tube AP patterning and the stereotypical emergence of organ identities, precede or are independent of a Hox code.”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Results > Emergence of organ identities
hedged- Asserted: passes — The authors put it forward as true.
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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
“Wherever possible, purity checks were performed indicating >99.9% sample purity.”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Methods > FACS
hedged- 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 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
“While we show that VE and DE descendants retain a signature of their lineage history, the data suggest they largely acquire transcriptomic equivalence.”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > DISCUSSION
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The entropy of these branch probabilities has been shown to represent a quantitative measure of the differentiation potential or plasticity of the cell, where multipotent cells have the highest differentiation potential and mature terminal states have the lowest potential.”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Methods > Palantir
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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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
“The investigators were not blinded to allocation during experiments and outcome assessment.”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Methods > Data reporting
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.
In the paper
“Hox gene expression in the developing central nervous system is considered a canonical descriptor of AP axis position46.”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Results > Emergence of organ identities
What the sources say
- Not checked — no full text of the sourcecites [46] Deschamps, J. & van Nes, J. Developmental regulation of the Hox genes during axial morphogenesis in the mouse. Development 132, 2931–2942 (2005). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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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
“The annotations and STAR parameters used for single cell RNA-seq data alignment were also used for bulk RNA-seq data to maintain consistency.”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Methods > Bulk RNA-seq processing
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
“All subcloned ISH probes were validated by sequencing.”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Methods > Amplification and cloning of antisense riboprobes
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
“Cellular suspensions were loaded on a Chromium Controller54 targeting a 2,500–10,000 cell range, depending on tissue type and embryo stage, to generate single cell 3’ RNA-seq libraries, in duplicate or triplicate.”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Methods > Single cell library preparation
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 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 data demonstrate that the VE is patterned at the onset of post-implantation development, and that the emVE, including the AVE subpopulation, are derivative of exVE.”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Results > Embryonic and extraembryonic visceral endoderm
boosteddirect- Asserted: passes — The authors put it forward as true.
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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, we noted a strong correlation in global gene expression patterns between VE and DE cells in binned locations along AP pseudo-space (Fig. 4b, purple), suggesting they were similarly patterned and acquiring regionalized organ-specific identities.”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Results > Anterior-Posterior patterning of gut endoderm
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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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
“Differences between consecutive time-points represent underlying developmental changes but are also confounded by technical batch effects, including discontinuity between E3.5 and E.4.5 and lack of spatial alignment between E6.5 and E7.5.”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Extended Data
plaincorrelational- 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
“Results validated in at least three independent experiments.”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Extended Data
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.
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
“Force directed layouts of context-independent targets of key signaling pathways acting within the endoderm lineage of the embryo.”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Extended Data
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.
- 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 paper relies on this without support.
The dynamics of key transcription factors and signaling pathway components within the ICM remain unclear.
“The dynamics of key TFs and signaling pathway components within the ICM remain unclear.”
The authors state this as an assumption.
Regions along pseudo-time where differentiation potential drops represent points where lineage specification and commitment occur.
“Regions along pseudo-time where DP drops represent points where lineage specification and commitment occur.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“PCA dimensionality reduction and mutual-nearest neighbours84 or Harmony34 batch correction was performed to correct for non-biological confounders between replicates and timepoints.”
From Cell diversity and plasticity during atrioventricular heart valve EMTs (2023) · cites this paper as [34]
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
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Results > A memory of extra-embryonic lineage history
“This classifier achieved near-perfect accuracy on E7.5 test data (auROC:0.96) (Extended Data Fig. 8h).”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Extended Data
“e, Receiver operating curve for classification of E7.5 VE and DE cells (4378 cells).”
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
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Results > Emergence of primitive endoderm
“Fgf5/Fgf8-Fgfr4 in emergent VE and Fgf3-Fgfr3 in ParE (Extended Data Fig. 5d, orange and black arrowheads).”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Extended Data
“Orange, black and green arrowheads point to high expression in ParE, VE and EPI, respectively.”
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
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Results > Emergence of organ identities
“VE descendant proportions in binned locations along the AP axis and AP pseudo-space axis were highly correlated (Extended Data Fig. 8m)”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Extended Data
“m, Same as l, for replicates of anterior-posterior cells (Replicate 1: 1821 cells, replicate 2: 1691 cells). Plots show the Pearson correlation.”
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
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Results > Emergence of organ identities
“Notably, DE and VE cells were predominantly primed towards anterior and posterior localization, respectively (Extended Data Fig. 8k, black arrowheads).”
§ The emergent landscape of the mouse gut endoderm at single-cell resolution > Extended Data
“k, Heatmap showing Pearson correlations between AP pseudo-space orderings determined using a varying number of diffusion components highlighting the robustness of the ordering.”
Citations
Cites
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STAR: ultrafast universal RNA-seq aligner
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Self-citation
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Sorted by citations
Deep learning and alignment of spatially resolved single-cell transcriptomes with Tangram
Biancalani, T., Scalia, G., Buffoni, L., Avasthi, R., Lu, Z., Sanger, A., Tokcan, N., Vanderburg, C. R., Segerstolpe, Å., Zhang, M., et al. (2021) · Nature Methods · doi:10.1038/s41592-021-01264-7 · Cited by 931
CellRank for directed single-cell fate mapping
Lange, M., Bergen, V., Klein, M., Setty, M. N., Reuter, B., Bakhti, M., Lickert, H., Ansari, M., Gote-Schniering, J., Schiller, H. B., et al. (2022) · Nature Methods · doi:10.1038/s41592-021-01346-6 · Cited by 783
“CellRank could also be extended by using temporal information, such as timepoints in the lung dataset 52 , to regularize the model, by only allowing transitions consistent with experimental time 64 .”
Self-citationLineage tracing meets single-cell omics: opportunities and challenges
Wagner, D. E., & Klein, A. M. (2020) · Nature Reviews Genetics · doi:10.1038/s41576-020-0223-2 · Cited by 617
Regenerative lineages and immune-mediated pruning in lung cancer metastasis
Laughney, A. M., Hu, J., Campbell, N. R., Bakhoum, S. F. W., Setty, M. N., Lavallée, V., Xie, Y., Masilionis, I., Carr, A., Kottapalli, S., et al. (2020) · Nature Medicine · doi:10.1038/s41591-019-0750-6 · Cited by 479
Self-citationLi, B., Zhang, W., Guo, C., Xu, H., Li, L., Fang, M., Hu, Y., Zhang, X., Yao, X., Tang, M., et al. (2022) · Nature Methods · doi:10.1038/s41592-022-01480-9 · Cited by 459
Metadata
- Authors
- Nowotschin, S., Setty, M., Kuo, Y.-Y., Liu, V., Garg, V., Sharma, R., Simon, C. S., Saiz, N., Gardner, R., Boutet, S. C., Church, D. M., Hoodless, P. A., Hadjantonakis, A.-K., & Pe’er, D.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- 10X Genomics (United States) (US)
- BC Cancer Agency (CA)
- Corresponding author
- Hadjantonakis, Anna-Katerina
- Pe’er, Dana
- ORCID
- Venue
- Nature
- Published
- 2019-04-08
- Volume
- 569
- Issue
- 7756
- Pages
- 361-367
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC6724221
- OpenAlex
- W2929173597
- Cited by
- 383
- References
- 57
- Citations by year
- 2026: 43 · 2025: 46 · 2024: 64 · 2023: 63 · 2022: 52 · 2021: 52 · 2020: 44 · 2019: 18
- FWCI
- 11.88
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institutes of Health (4r01ca164729-05)
- National Cancer Institute (R01-CA164729, P30CA008748)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK084391)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (DP1HD084071, R01HD094868)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Keywords
- gut endoderm, mouse embryo, single-cell transcriptomics, extraembryonic endoderm, primitive endoderm, gastrulation, cell differentiation trajectories, anterior-posterior axis, lineage history
- MeSH terms
- Animals, Blastocyst, Cell Differentiation, Endoderm, Female, Intestines, Male, Cell Lineage, Body Patterning, Mice, Gastrulation, Single-Cell Analysis
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 2026-10-23, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-23 (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 ›
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