Evidence map›Paper›PMID 35411086›Full record

ArticleNature cell biology2022

Sequential enhancer state remodelling defines human germline competence and specification.

Walfred W C Tang, Aracely Castillo-Venzor, Wolfram H Gruhn, Toshihiro Kobayashi, Christopher A Penfold, Michael D Morgan, Dawei Sun, Naoko Irie, M Azim Surani

Open access · greenAbstract read
In one paragraph

Article in Nature cell biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
5.8field-weighted citation impact, top 3% 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

48 citing papers in PubMed, 69 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Mechanisms of human germ cell development.Nature reviews. Molecular cell biology · 2026
    Review
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  16. Jund orchestratesProceedings of the National Academy of Sciences of the United States of America · 2025
    Article
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  20. Review
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

9 authors at 4 institutions in 2 countries.

Walfred W C Tang *Wellcome Trust/Cancer Research UK Gurdon Institute, Henry Wellcome Building of Cancer and Developmental Biology, Cambridge, UK. walfredtang@gmail.com.ORCID http://orcid.org/0000-0002-5803-1681
Aracely Castillo-Venzor *Wellcome Trust/Cancer Research UK Gurdon Institute, Henry Wellcome Building of Cancer and Developmental Biology, Cambridge, UK.ORCID http://orcid.org/0000-0002-2288-2679
Wolfram H Gruhn *Wellcome Trust/Cancer Research UK Gurdon Institute, Henry Wellcome Building of Cancer and Developmental Biology, Cambridge, UK.ORCID http://orcid.org/0000-0001-6072-1916
Toshihiro KobayashiDivision of Mammalian Embryology, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Christopher A PenfoldWellcome Trust/Cancer Research UK Gurdon Institute, Henry Wellcome Building of Cancer and Developmental Biology, Cambridge, UK.
Michael D MorganCancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge, UK.
Dawei SunWellcome Trust/Cancer Research UK Gurdon Institute, Henry Wellcome Building of Cancer and Developmental Biology, Cambridge, UK.
Naoko IrieWellcome Trust/Cancer Research UK Gurdon Institute, Henry Wellcome Building of Cancer and Developmental Biology, Cambridge, UK.
M Azim SuraniWellcome Trust/Cancer Research UK Gurdon Institute, Henry Wellcome Building of Cancer and Developmental Biology, Cambridge, UK. a.surani@gurdon.cam.ac.uk.ORCID http://orcid.org/0000-0002-8640-4318
University of Cambridge · GBWellcome/MRC Cambridge Stem Cell Institute · GBEuropean Bioinformatics Institute · GBNational Institute for Physiological Sciences · JP

Funding

Biotechnology and Biological Sciences Research Council BB/T01346X/1Biotechnology and Biological Sciences Research Council G103986Medical Research Council MR/P009948/1Medical Research Council RG85305Wellcome Trust 096738Wellcome Trust 109146Wellcome Trust 203831Wellcome Trust 209475Wellcome Trust 209475/Z/17/ZWellcome Trust (Wellcome) 203831/Z/16/Z
6 · The paper itself

Abstract

Germline-soma segregation is a fundamental event during mammalian embryonic development. Here we establish the epigenetic principles of human primordial germ cell (hPGC) development using in vivo hPGCs and stem cell models recapitulating gastrulation. We show that morphogen-induced remodelling of mesendoderm enhancers transiently confers the competence for hPGC fate, but further activation favours mesoderm and endoderm fates. Consistently, reducing the expression of the mesendodermal transcription factor OTX2 promotes the PGC fate. In hPGCs, SOX17 and TFAP2C initiate activation of enhancers to establish a core germline programme, including the transcriptional repressor PRDM1 and pluripotency factors POU5F1 and NANOG. We demonstrate that SOX17 enhancers are the critical components in the regulatory circuitry of germline competence. Furthermore, activation of upstream cis-regulatory elements by an optimized CRISPR activation system is sufficient for hPGC specification. We reveal an enhancer-linked germline transcription factor network that provides the basis for the evolutionary divergence of mammalian germlines.

Indexed as

GastrulationGerm CellsAnimalsCell DifferentiationEmbryonic DevelopmentEndodermGene Expression Regulation, DevelopmentalHumansMammals

Identifiers

PMID35411086
PMCPMC7612729
OpenAlexW4223498821

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.