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Publication : WTAP Function in Sertoli Cells Is Essential for Sustaining the Spermatogonial Stem Cell Niche.

First Author  Jia GX Year  2020
Journal  Stem Cell Reports Volume  15
Issue  4 Pages  968-982
PubMed ID  33053361 Mgi Jnum  J:299024
Mgi Id  MGI:6489618 Doi  10.1016/j.stemcr.2020.09.001
Citation  Jia GX, et al. (2020) WTAP Function in Sertoli Cells Is Essential for Sustaining the Spermatogonial Stem Cell Niche. Stem Cell Reports 15(4):968-982
abstractText  Sertoli cells are the major component of the spermatogonial stem cell (SSC) niche; however, regulatory mechanisms in Sertoli cells that dictate SSC fate decisions remain largely unknown. Here we revealed features of the N(6)-methyladenosine (m(6)A) mRNA modification in Sertoli cells and demonstrated the functions of WTAP, the key subunit of the m(6)A methyltransferase complex in spermatogenesis. m(6)A-sequencing analysis identified 21,909 m(6)A sites from 15,365 putative m(6)A-enriched transcripts within 6,122 genes, including many Sertoli cell-specific genes. Conditional deletion of Wtap in Sertoli cells resulted in sterility and the progressive loss of the SSC population. RNA sequencing and ribosome nascent-chain complex-bound mRNA sequencing analyses suggested that alternative splicing events of transcripts encoding SSC niche factors were sharply altered and translation of these transcripts were severely dysregulated by Wtap deletion. Collectively, this study uncovers a novel regulatory mechanism of the SSC niche and provide insights into molecular interactions between stem cells and their cognate niches in mammals.
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