Evidence map›Paper›PMID 26751055›Full record

ArticleNature2016

NANOG alone induces germ cells in primed epiblast in vitro by activation of enhancers.

Kazuhiro Murakami, Ufuk Günesdogan, Jan J Zylicz, Walfred W C Tang, Roopsha Sengupta, Toshihiro Kobayashi, Shinseog Kim, Richard Butler, Sabine Dietmann, M Azim Surani

Abstract read
In one paragraph

Article in Nature, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers.

0numbers the graph read from it
0cells of the map it votes in
104citing papers in PubMed
13.8field-weighted citation impact, top 1% 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

104 citing papers in PubMed, 193 citations in OpenAlex.

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  14. DNMT1 can induce primary germ layer differentiation through de novo DNA methylation.Genes to cells : devoted to molecular & cellular mechanisms · 2024
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44 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

10 authors at 5 institutions in 2 countries.

Kazuhiro Murakami *Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
Ufuk Günesdogan *Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
Jan J ZyliczWellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
Walfred W C TangWellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
Roopsha SenguptaWellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
Toshihiro KobayashiWellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
Shinseog KimWellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
Richard ButlerWellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
Sabine DietmannWellcome Trust Medical Research Council Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK.
M Azim SuraniWellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
Wellcome/Cancer Research UK Gurdon Institute · GBMedical Research Council · GBWellcome Trust · GBHokkaido University · JPWellcome/MRC Cambridge Stem Cell Institute · GB

Funding

Cancer Research UK C6946/A14492Medical Research Council MC_PC_12009Wellcome Trust 092096Wellcome Trust 096738Wellcome Trust RG44593
6 · The paper itself

Abstract

Nanog, a core pluripotency factor in the inner cell mass of blastocysts, is also expressed in unipotent primordial germ cells (PGCs) in mice, where its precise role is yet unclear. We investigated this in an in vitro model, in which naive pluripotent embryonic stem (ES) cells cultured in basic fibroblast growth factor (bFGF) and activin A develop as epiblast-like cells (EpiLCs) and gain competence for a PGC-like fate. Consequently, bone morphogenetic protein 4 (BMP4), or ectopic expression of key germline transcription factors Prdm1, Prdm14 and Tfap2c, directly induce PGC-like cells (PGCLCs) in EpiLCs, but not in ES cells. Here we report an unexpected discovery that Nanog alone can induce PGCLCs in EpiLCs, independently of BMP4. We propose that after the dissolution of the naive ES-cell pluripotency network during establishment of EpiLCs, the epigenome is reset for cell fate determination. Indeed, we found genome-wide changes in NANOG-binding patterns between ES cells and EpiLCs, indicating epigenetic resetting of regulatory elements. Accordingly, we show that NANOG can bind and activate enhancers of Prdm1 and Prdm14 in EpiLCs in vitro; BLIMP1 (encoded by Prdm1) then directly induces Tfap2c. Furthermore, while SOX2 and NANOG promote the pluripotent state in ES cells, they show contrasting roles in EpiLCs, as Sox2 specifically represses PGCLC induction by Nanog. This study demonstrates a broadly applicable mechanistic principle for how cells acquire competence for cell fate determination, resulting in the context-dependent roles of key transcription factors during development.

Indexed as

ActivinsAnimalsBone Morphogenetic Protein 4Cell DifferentiationChromatinDNA-Binding ProteinsEnhancer Elements, GeneticEpigenesis, GeneticFemaleFibroblast Growth Factor 2Gene Expression Regulation, DevelopmentalGenomeGerm CellsGerm LayersHomeodomain ProteinsMaleactivin AActivinsBmp4 protein, mouseBone Morphogenetic Protein 4ChromatinDNA-Binding ProteinsFibroblast Growth Factor 2Homeodomain ProteinsNanog Homeobox ProteinNanog protein, mousePositive Regulatory Domain I-Binding Factor 1Prdm14 protein, mousePrdm1 protein, mouseRNA-Binding ProteinsSox2 protein, mouseSOXB1 Transcription FactorsTfap2c protein, mouseTranscription Factor AP-2Transcription Factors

Identifiers

PMID26751055
PMCPMC4724940
OpenAlexW2238949050

What OpenQuestion holds

Textmetadata
LicenceTDM
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.