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RHOX10 Drives Mouse Spermatogonial Stem Cell Establishment Through A Transcription Factor Signaling Cascade

ABSTRACT: Spermatogonial stem cells (SSCs) are essential for male fertility. Here, we report that mouse SSC generation is driven by a transcription factor (TF) cascade controlled by the homeobox protein, RHOX10, which acts by stimulating the differentiation of SSC precursors called pro-spermatogonia (ProSG). We identify genes regulated by RHOX10 in ProSG in vivo, and define direct RHOX10-target genes using several approaches, including a rapid temporal induction assay we design: iSLAMseq. Together, these approaches identify temporal waves of direct targets, as well as secondary-target genes. Many of the RHOX10-regulated genes encode proteins with known roles in SSCs. Using an in vitro ProSG differentiation assay that we develop, we find that RHOX10 promotes mouse ProSG differentiation through a conserved transcriptional cascade involving the key germ-cell TFs DMRT1 and ZBTB16. Our study gives important insights into germ cell development and provides a blueprint for how to define TF cascades.

ORGANISM(S): Mus musculus

PROVIDER: GSE165372 | GEO | 2021/06/18

REPOSITORIES: GEO

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