Evidence map›Paper›PMID 22791892›Full record

ArticleDevelopment (Cambridge, England)2012

Conversion from mouse embryonic to extra-embryonic endoderm stem cells reveals distinct differentiation capacities of pluripotent stem cell states.

Lily T Y Cho, Sissy E Wamaitha, Isheng J Tsai, Jérôme Artus, Richard I Sherwood, Roger A Pedersen, Anna-Katerina Hadjantonakis, Kathy K Niakan

Open access · bronzeAbstract read
In one paragraph

Article in Development (Cambridge, England), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed
3.8field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

64 citing papers in PubMed, 109 citations in OpenAlex.

  1. Article
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  8. Article
  9. Capture of Totipotency in Mouse Embryonic Stem Cells in the Absence of Pdzk1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  10. Review
  11. Article
  12. Article
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  15. Review
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  17. Review
  18. Article
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  20. Article

4 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 4 institutions in 2 countries.

Lily T Y ChoThe Anne McLaren Laboratory for Regenerative Medicine, Stem Cell Institute, University of Cambridge, Cambridge CB2 0SZ, UK.
Sissy E Wamaitha
Isheng J Tsai
Jérôme Artus
Richard I Sherwood
Roger A Pedersen
Anna-Katerina Hadjantonakis
Kathy K Niakan
University of Cambridge · GBKettering University · USHarvard University · USWellcome Sanger Institute · GB

Funding

Morphogenesis of the paraxial mesoderm in miceR01HD052115 · NICHD · SLOAN-KETTERING INST CAN RESEARCH · PI HADJANTONAKIS, ANNA-KATERINA · 2006 to 2015
$4.1M
Morphogenesis of mammalian gut endodermR01DK084391 · NIDDK · SLOAN-KETTERING INST CAN RESEARCH · PI HADJANTONAKIS, ANNA-KATERINA · 2009 to 2018
$4.1M
Medical Research Council G0600275Medical Research Council G0800784NICHD NIH HHS R01 HD052115NICHD NIH HHS R01-HD052115NIDDK NIH HHS R01 DK084391NIDDK NIH HHS R01-DK084391Wellcome Trust 079249
6 · The paper itself

Abstract

The inner cell mass of the mouse pre-implantation blastocyst comprises epiblast progenitor and primitive endoderm cells of which cognate embryonic (mESCs) or extra-embryonic (XEN) stem cell lines can be derived. Importantly, each stem cell type retains the defining properties and lineage restriction of their in vivo tissue of origin. Recently, we demonstrated that XEN-like cells arise within mESC cultures. This raises the possibility that mESCs can generate self-renewing XEN cells without the requirement for gene manipulation. We have developed a novel approach to convert mESCs to XEN cells (cXEN) using growth factors. We confirm that the downregulation of the pluripotency transcription factor Nanog and the expression of primitive endoderm-associated genes Gata6, Gata4, Sox17 and Pdgfra are necessary for cXEN cell derivation. This approach highlights an important function for Fgf4 in cXEN cell derivation. Paracrine FGF signalling compensates for the loss of endogenous Fgf4, which is necessary to exit mESC self-renewal, but not for XEN cell maintenance. Our cXEN protocol also reveals that distinct pluripotent stem cells respond uniquely to differentiation promoting signals. cXEN cells can be derived from mESCs cultured with Erk and Gsk3 inhibitors (2i), and LIF, similar to conventional mESCs. However, we find that epiblast stem cells (EpiSCs) derived from the post-implantation embryo are refractory to cXEN cell establishment, consistent with the hypothesis that EpiSCs represent a pluripotent state distinct from mESCs. In all, these findings suggest that the potential of mESCs includes the capacity to give rise to both extra-embryonic and embryonic lineages.

Indexed as

ActivinsAnimalsBone Morphogenetic Protein 4Cell DifferentiationCell LineageCells, CulturedEmbryonic Stem CellsEndodermFibroblast Growth Factor 4GATA4 Transcription FactorGATA6 Transcription FactorGene Expression Regulation, DevelopmentalHMGB ProteinsMiceMice, KnockoutMice, TransgenicActivinsBmp4 protein, mouseBone Morphogenetic Protein 4Fgf4 protein, mouseFibroblast Growth Factor 4Gata4 protein, mouseGATA4 Transcription FactorGata6 protein, mouseGATA6 Transcription FactorHMGB ProteinsReceptor, Platelet-Derived Growth Factor alphaSox17 protein, mouseSOXF Transcription FactorsTretinoin

Identifiers

PMID22791892
PMCPMC3403099
OpenAlexW2107167447

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.