is Required for Male Germ Cell Development and Spermatogonial Stem Cell Maintenance

Overview

Journal bioRxiv

Date 2023 Oct 24

PMID 37873304

Authors

Qing Chen

Safia Malki

Xiaojiang Xu

Brian Bennett

Brad L Lackford

Oleksandr Kirsanov

Christopher B Geyer

Guang Hu

Affiliations

Soon will be listed here.

Abstract

The foundation of spermatogenesis and lifelong fertility is provided by spermatogonial stem cells (SSCs). SSCs divide asymmetrically to either replenish their numbers (self-renewal) or produce undifferentiated progenitors that proliferate before committing to differentiation. However, regulatory mechanisms governing SSC maintenance are poorly understood. Here, we show that the CCR4-NOT mRNA deadenylase complex subunit CNOT3 plays a critical role in maintaining spermatogonial populations in mice. is highly expressed in undifferentiated spermatogonia, and its deletion in spermatogonia resulted in germ cell loss and infertility. Single cell analyses revealed that deletion led to the de-repression of transcripts encoding factors involved in spermatogonial differentiation, including those in the glutathione redox pathway that are critical for SSC maintenance. Together, our study reveals that CNOT3 - likely via the CCR4-NOT complex - actively degrades transcripts encoding differentiation factors to sustain the spermatogonial pool and ensure the progression of spermatogenesis, highlighting the importance of CCR4-NOT-mediated post-transcriptional gene regulation during male germ cell development.

Citing Articles

mRNA stability fine-tunes gene expression in the developing cortex to control neurogenesis.

Serdar L, Egol J, Lackford B, Bennett B, Hu G, Silver D PLoS Biol. 2025; 23(2):e3003031.

PMID: 39913536 PMC: 11838918. DOI: 10.1371/journal.pbio.3003031.

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