Evidence map›Paper›PMID 40814964›Full record

ArticleDevelopment (Cambridge, England)2025

Cnot3 is required for male germ cell development and spermatogonial stem cell maintenance.

Qing Chen, Safia Malki, Xiaojiang Xu, Jiajia Wang, Brian Bennett, Xiaofeng Zheng, Brad L Lackford, Oleksandr Kirsanov, Christopher B Geyer, Guang Hu

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Development (Cambridge, England), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Poly(A) tail regulation in stem cells and early development.Cell regeneration (London, England) · 2025
    Review
  3. Article
4 · The record

Corrections and comments

  • Update of
    2023
5 · Who and what money

Authors and funding

10 authors.

Qing ChenEpigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
Safia MalkiEpigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.ORCID 0000-0002-5193-5581
Xiaojiang XuIntegrative Bioinformatics Support Group, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
Jiajia WangEpigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
Brian BennettIntegrative Bioinformatics Support Group, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
Xiaofeng ZhengSchool of Veterinary Medicine, Hunan Agricultural University, Changsha, Hunan 410127, China.
Brad L LackfordEpigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
Oleksandr KirsanovDepartment of Anatomy & Cell Biology, Brody School of Medicine at East Carolina University, Greenville, NC 27834, USA.
Christopher B GeyerDepartment of Anatomy & Cell Biology, Brody School of Medicine at East Carolina University, Greenville, NC 27834, USA.
Guang HuEpigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.

Funding

Challenging the role of retinoic acid in meiotic initiationR21HD105963 · NICHD · EAST CAROLINA UNIVERSITY · PI GEYER, CHRISTOPHER BENNETT · 2022 to 2023
$424k
NICHD NIH HHS R21 HD105963NIEHS NIH HHSNIH HHS R01HD09003NIH HHS R21HD105963Z01ES102745
6 · The paper itself

Abstract

The foundation of spermatogenesis and lifelong fertility is provided by spermatogonial stem cells (SSCs). SSCs divide asymmetrically to either self-renew or produce undifferentiated progenitors. However, regulatory mechanisms governing SSC maintenance are poorly understood. Here, we show that the CCR4-NOT mRNA deadenylase complex subunit CNOT3 is essential for sustaining spermatogonial populations in mice. Its deletion in adult germ cells resulted in germ cell loss and infertility, and its deletion in spermatogonia in the developing testis resulted in SSC depletion and compromised spermatogenesis. Consistent with the in vivo results, deletion of Cnot3 in cultured SSCs caused a reduction in cell proliferation and viability, and downregulation of SSC markers. Mechanistically, Cnot3 deletion led to the de-repression of transcripts encoding factors involved in spermatogonial differentiation, including those in the glutathione redox pathway that are crucial for SSC maintenance. Together, our study reveals that CNOT3 - likely via the CCR4-NOT complex - promotes the degradation of transcripts encoding differentiation factors to maintain the SSCs in the stem cell state, highlighting the importance of CCR4-NOT-mediated post-transcriptional gene regulation in SSCs and male germ cell development.

Indexed as

Adult Germline Stem CellsSpermatogenesisSpermatogoniaStem CellsTranscription FactorsAnimalsCell DifferentiationCell ProliferationGene Expression Regulation, DevelopmentalMaleMiceMice, Inbred C57BLMice, KnockoutTestisCNOT3 protein, mouseTranscription FactorsGlutathione redox pathwayMaintenanceMousescRNA-seqSpermatogenesisSpermatogonial stem cells

Identifiers

PMID40814964
PMCPMC12401510

What OpenQuestion holds

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LicenceCC BY
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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.