Journal
CELL REPORTS
Volume 36, Issue 3, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2021.109423
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Funding
- NIH [R01 GM119128]
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The generation of mouse Spermatogonial Stem Cells (SSCs) is driven by a transcription factor (TF) cascade controlled by the homeobox protein, RHOX10. This cascade involves the differentiation of SSC precursors and the identification of RHOX10-regulated genes associated with SSC development. The study provides important insights into germ cell development and how transcription factor cascades are defined.
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 driving 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: iSLAMseq. Together, these approaches identify temporal waves of RHOX10 direct targets, as well as RHOX10 secondary-target genes. Many of the RHOX10-regulated genes encode proteins with known roles in SSCs. Using an in vitro ProSG differentiation assay, 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.
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