Evidence map›Paper›PMID 27015307›Full record

ArticleCell2016

Heterogeneity in Oct4 and Sox2 Targets Biases Cell Fate in 4-Cell Mouse Embryos.

Mubeen Goolam, Antonio Scialdone, Sarah J L Graham, Iain C Macaulay, Agnieszka Jedrusik, Anna Hupalowska, Thierry Voet, John C Marioni, Magdalena Zernicka-Goetz

Open access · hybridAbstract read
In one paragraph

Article in Cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 221 papers.

0numbers the graph read from it
0cells of the map it votes in
221citing papers in PubMed
31.3field-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

221 citing papers in PubMed, 515 citations in OpenAlex.

  1. Interpretable scRNA-seq Analysis with Intelligent Gene Selection.Applied biochemistry and biotechnology · 2026
    Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Subcellularly Resolved 3D Translatome in Mouse Oocytes and Early Embryos.bioRxiv : the preprint server for biology · 2026
    Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. What makes genes burst.Trends in cell biology · 2026
    Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 2 countries.

Mubeen GoolamDepartment of Physiology, Development & Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK.
Antonio ScialdoneEuropean Bioinformatics Institute, European Molecular Biology Laboratory (EMBL-EBI), Wellcome Genome Campus, Cambridge CB10 1SD, UK; Wellcome Trust Sanger Institute, Wellcome Genome Campus, Cambridge CB10 1SA, UK.
Sarah J L GrahamDepartment of Physiology, Development & Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK.
Iain C MacaulayWellcome Trust Sanger Institute, Wellcome Genome Campus, Cambridge CB10 1SA, UK.
Agnieszka JedrusikDepartment of Physiology, Development & Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK.
Anna HupalowskaDepartment of Physiology, Development & Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK.
Thierry VoetWellcome Trust Sanger Institute, Wellcome Genome Campus, Cambridge CB10 1SA, UK; Laboratory of Reproductive Genomics, Department of Human Genetics, KU Leuven, Herestraat 49, 3000 Leuven, Belgium.
John C MarioniEuropean Bioinformatics Institute, European Molecular Biology Laboratory (EMBL-EBI), Wellcome Genome Campus, Cambridge CB10 1SD, UK; Wellcome Trust Sanger Institute, Wellcome Genome Campus, Cambridge CB10 1SA, UK; Cancer Research UK-Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge CB2 0RE, UK. Electronic address: marioni@ebi.ac.uk.
Magdalena Zernicka-GoetzDepartment of Physiology, Development & Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK. Electronic address: mz205@cam.ac.uk.
University of Cambridge · GBWellcome Sanger Institute · GBEuropean Bioinformatics Institute · GB

Funding

Cancer Research UK 22231Wellcome Trust
6 · The paper itself

Abstract

The major and essential objective of pre-implantation development is to establish embryonic and extra-embryonic cell fates. To address when and how this fundamental process is initiated in mammals, we characterize transcriptomes of all individual cells throughout mouse pre-implantation development. This identifies targets of master pluripotency regulators Oct4 and Sox2 as being highly heterogeneously expressed between blastomeres of the 4-cell embryo, with Sox21 showing one of the most heterogeneous expression profiles. Live-cell tracking demonstrates that cells with decreased Sox21 yield more extra-embryonic than pluripotent progeny. Consistently, decreasing Sox21 results in premature upregulation of the differentiation regulator Cdx2, suggesting that Sox21 helps safeguard pluripotency. Furthermore, Sox21 is elevated following increased expression of the histone H3R26-methylase CARM1 and is lowered following CARM1 inhibition, indicating the importance of epigenetic regulation. Therefore, our results indicate that heterogeneous gene expression, as early as the 4-cell stage, initiates cell-fate decisions by modulating the balance of pluripotency and differentiation.

Indexed as

Gene Expression Regulation, DevelopmentalAnimalsBlastocystCARD Signaling Adaptor ProteinsCDX2 Transcription FactorEmbryo, MammalianEpigenesis, GeneticGene Expression ProfilingGene Regulatory NetworksHomeodomain ProteinsMiceOctamer Transcription Factor-3Pluripotent Stem CellsSingle-Cell AnalysisSOXB1 Transcription FactorsSOXB2 Transcription FactorsCard11 protein, mouseCARD Signaling Adaptor ProteinsCdx2 protein, mouseCDX2 Transcription FactorHomeodomain ProteinsOctamer Transcription Factor-3Pou5f1 protein, mouseSox21 protein, mouseSox2 protein, mouseSOXB1 Transcription FactorsSOXB2 Transcription FactorsTranscription Factors

Identifiers

PMID27015307
PMCPMC4819611
OpenAlexW2307567449

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.