Evidence map›Paper›PMID 22367759›Full record

ArticleStem cells (Dayton, Ohio)2012

Cnot1, Cnot2, and Cnot3 maintain mouse and human ESC identity and inhibit extraembryonic differentiation.

Xiaofeng Zheng, Raluca Dumitru, Brad L Lackford, Johannes M Freudenberg, Ajeet P Singh, Trevor K Archer, Raja Jothi, Guang Hu

Abstract read
In one paragraph

Article in Stem cells (Dayton, Ohio), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed
–field-weighted citation impact
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

46 citing papers in PubMed.

  1. Article
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  6. Poly(A) tail regulation in stem cells and early development.Cell regeneration (London, England) · 2025
    Review
  7. Article
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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

8 authors.

Xiaofeng ZhengLaboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, RTP, North Carolina, USA.
Raluca Dumitru
Brad L Lackford
Johannes M Freudenberg
Ajeet P Singh
Trevor K Archer
Raja Jothi
Guang Hu

Funding

Transcriptional Functions of Nuclear Receptors in Cancer CellsZIAES071006 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI ARCHER, TREVOR KEITH · 2009 to 2025
$58.0M
Gene Expression and MicroarraysZICES102445 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI GERRISH, KEVIN · 2009 to 2025
$31.6M
Role of Pluripotency Factors in Pluripotent Stem Cells, Development and DiseaseZIAES102745 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI HU, GUANG · 2010 to 2025
$31.5M
Gene regulatory elements, networks, and mechanismsZIAES102625 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI JOTHI, RAJA · 2009 to 2025
$27.4M
Transcriptional Functions of Nuclear Receptors in Cancer CellsZ01ES071006 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI ARCHER, TREVOR KEITH · 1999 to 2008
$6.9M
Intramural NIH HHS Z01 ES071006Intramural NIH HHS ZIA ES102625Intramural NIH HHS ZIA ES102745NIEHS NIH HHS Z01ES071006-11NIEHS NIH HHS Z01ES102745PHS HHS 1ZIAES102625
6 · The paper itself

Abstract

Embryonic stem cell (ESC) identity and self-renewal is maintained by extrinsic signaling pathways and intrinsic gene regulatory networks. Here, we show that three members of the Ccr4-Not complex, Cnot1, Cnot2, and Cnot3, play critical roles in maintaining mouse and human ESC identity as a protein complex and inhibit differentiation into the extraembryonic lineages. Enriched in the inner cell mass of blastocysts, these Cnot genes are highly expressed in ESC and downregulated during differentiation. In mouse ESCs, Cnot1, Cnot2, and Cnot3 are important for maintenance in both normal conditions and the 2i/LIF medium that supports the ground state pluripotency. Genetic analysis indicated that they do not act through known self-renewal pathways or core transcription factors. Instead, they repress the expression of early trophectoderm (TE) transcription factors such as Cdx2. Importantly, these Cnot genes are also necessary for the maintenance of human ESCs, and silencing them mainly lead to TE and primitive endoderm differentiation. Together, our results indicate that Cnot1, Cnot2, and Cnot3 represent a novel component of the core self-renewal and pluripotency circuitry conserved in mouse and human ESCs.

Indexed as

AnimalsCell DifferentiationCell LineEmbryonic Stem CellsGene SilencingHumansMiceMice, KnockoutPluripotent Stem CellsRepressor ProteinsTranscription FactorsCNOT1 protein, humanCNOT2 protein, humanCNOT3 protein, humanCNOT3 protein, mouseRepressor ProteinsTranscription Factors

Identifiers

PMID22367759
PMCPMC3787717

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Registered trials

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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.