DNMT3A-dependent DNA methylation is required for spermatogonial stem cells to commit to spermatogenesis
DNMT3A-dependent DNA methylation is required for spermatogonial stem cells to commit to spermatogenesis
Abstract DNA methylation plays a critical role in spermatogenesis, as evidenced by the male sterility of DNA methyltransferase (DNMT) mutant mice. Here, we report a striking division of labor in the establishment of the methylation landscape of male germ cells and its functions in spermatogenesis: while DNMT3C is essential for preventing retrotransposons from interfering with meiosis, DNMT3A broadly methylates the genome—at the exception of DNMT3C-dependent retrotransposons—and controls spermatogonial stem cell (SSC) plasticity. By reconstructing developmental trajectories through single-cell RNA-seq and by profiling chromatin states, we found that Dnmt3A mutant SSCs can only self-renew and no longer differentiate due to spurious enhancer activation that enforces an irreversible stem cell gene program. We therefore provide a novel function for DNA methylation in male fertility: the epigenetic programming of SSC commitment to differentiation and to life-long spermatogenesis supply.
Bourc?ˉhis Deborah、Dura Mathilde、Armand M¨|lanie、Bonneville Lorraine、Weber Michael、Lameiras Sonia、Barau Joan、Baudrin Laura G.、Teissandier Aur¨|lie
Genetics and Developmental Biology Department, Institut Curie, PSL Research University, INSERMGenetics and Developmental Biology Department, Institut Curie, PSL Research University, INSERMGenetics and Developmental Biology Department, Institut Curie, PSL Research University, INSERMGenetics and Developmental Biology Department, Institut Curie, PSL Research University, INSERMBiotechnology and Cell Signaling, University of StrasbourgICGex Next-Generation Sequencing platform, Institut Curie, PSL Research UniversityInstitute of Molecular Biology (IMB)ICGex Next-Generation Sequencing platform, Institut Curie, PSL Research UniversityGenetics and Developmental Biology Department, Institut Curie, PSL Research University, INSERM
遗传学细胞生物学分子生物学
Bourc?ˉhis Deborah,Dura Mathilde,Armand M¨|lanie,Bonneville Lorraine,Weber Michael,Lameiras Sonia,Barau Joan,Baudrin Laura G.,Teissandier Aur¨|lie.DNMT3A-dependent DNA methylation is required for spermatogonial stem cells to commit to spermatogenesis[EB/OL].(2025-03-28)[2025-08-02].https://www.biorxiv.org/content/10.1101/2021.04.19.440465.点此复制
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