Qing Chen, Safia Malki, Xiaojiang Xu, Jiajia Wang, Brian Bennett, Xiaofeng Zheng, Brad L Lackford, Oleksandr Kirsanov, Christopher B Geyer, Guang Hu
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引用次数: 0
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.
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Development’s scope covers all aspects of plant and animal development, including stem cell biology and regeneration. The single most important criterion for acceptance in Development is scientific excellence. Research papers (articles and reports) should therefore pose and test a significant hypothesis or address a significant question, and should provide novel perspectives that advance our understanding of development. We also encourage submission of papers that use computational methods or mathematical models to obtain significant new insights into developmental biology topics. Manuscripts that are descriptive in nature will be considered only when they lay important groundwork for a field and/or provide novel resources for understanding developmental processes of broad interest to the community.
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