Evidence map›Paper›PMID 34463252›Full record

ArticleeLife2021

TGFβ signalling is required to maintain pluripotency of human naïve pluripotent stem cells.

Anna Osnato, Stephanie Brown, Christel Krueger, Simon Andrews, Amanda J Collier, Shota Nakanoh, Mariana Quiroga Londoño, Brandon T Wesley, Daniele Muraro, A Sophie Brumm and 4 more

Open access · goldAbstract read
In one paragraph

Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
2.9field-weighted citation impact, top 8% 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

38 citing papers in PubMed, 58 citations in OpenAlex.

  1. Review
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  5. The Influences of RARγ on the Behavior of Normal and Cancer Stem Cells.International journal of molecular sciences · 2026
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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

14 authors at 5 institutions in 2 countries.

Anna OsnatoWellcome-MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, United Kingdom.ORCID 0000-0001-5241-1512
Stephanie BrownWellcome-MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, United Kingdom.
Christel KruegerBioinformatics Group, The Babraham Institute, Cambridge, United Kingdom.ORCID 0000-0001-5601-598X
Simon AndrewsBioinformatics Group, The Babraham Institute, Cambridge, United Kingdom.ORCID 0000-0002-5006-3507
Amanda J CollierEpigenetics Programme, The Babraham Institute, Cambridge, United Kingdom.ORCID 0000-0003-1137-6874
Shota NakanohWellcome-MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, United Kingdom.
Mariana Quiroga LondoñoWellcome-MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, United Kingdom.ORCID 0000-0003-2352-0773
Brandon T WesleyWellcome-MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, United Kingdom.
Daniele MuraroWellcome-MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, United Kingdom.
A Sophie BrummHuman Embryo and Stem Cell Laboratory, The Francis Crick Institute, London, United Kingdom.
Kathy K NiakanHuman Embryo and Stem Cell Laboratory, The Francis Crick Institute, London, United Kingdom.ORCID 0000-0003-1646-4734
Ludovic Vallier *Wellcome-MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, United Kingdom.ORCID 0000-0002-3848-2602
Daniel Ortmann *Wellcome-MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, United Kingdom.
Peter J Rugg-Gunn *Wellcome-MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, United Kingdom.ORCID 0000-0002-9601-5949
Wellcome/MRC Cambridge Stem Cell Institute · GBBabraham Institute · GBNational Institute for Basic Biology · JPThe Francis Crick Institute · GBUniversity of Cambridge · GB

Funding

Biotechnology and Biological Sciences Research Council BBS/E/B/000C0421Biotechnology and Biological Sciences Research Council BBS/E/B/000C0422Cancer Research UK FC001120Department of HealthMedical Research Council MC_PC_17230Medical Research Council MR/J003808/1Medical Research Council MR/T011769/1Medical Research Council MR/V02969X/1Wellcome Trust
6 · The paper itself

Abstract

The signalling pathways that maintain primed human pluripotent stem cells (hPSCs) have been well characterised, revealing a critical role for TGFβ/Activin/Nodal signalling. In contrast, the signalling requirements of naive human pluripotency have not been fully established. Here, we demonstrate that TGFβ signalling is required to maintain naive hPSCs. The downstream effector proteins - SMAD2/3 - bind common sites in naive and primed hPSCs, including shared pluripotency genes. In naive hPSCs, SMAD2/3 additionally bind to active regulatory regions near to naive pluripotency genes. Inhibiting TGFβ signalling in naive hPSCs causes the downregulation of SMAD2/3-target genes and pluripotency exit. Single-cell analyses reveal that naive and primed hPSCs follow different transcriptional trajectories after inhibition of TGFβ signalling. Primed hPSCs differentiate into neuroectoderm cells, whereas naive hPSCs transition into trophectoderm. These results establish that there is a continuum for TGFβ pathway function in human pluripotency spanning a developmental window from naive to primed states.

Indexed as

Cell DifferentiationCell LineCellular ReprogrammingHumansPluripotent Stem CellsSignal TransductionSmad2 ProteinSmad3 ProteinTransforming Growth Factor betaSmad2 ProteinSMAD2 protein, humanSmad3 ProteinSMAD3 protein, humanTransforming Growth Factor betaembryonic stem cellsgene regulationhumanpluripotent stem cellsregenerative medicinestem cells

Identifiers

PMID34463252
PMCPMC8410071
OpenAlexW3198668746

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.