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Publication : RHOX10 drives mouse spermatogonial stem cell establishment through a transcription factor signaling cascade.

First Author  Tan K Year  2021
Journal  Cell Rep Volume  36
Issue  3 Pages  109423
PubMed ID  34289349 Mgi Jnum  J:321452
Mgi Id  MGI:6876942 Doi  10.1016/j.celrep.2021.109423
Citation  Tan K, et al. (2021) RHOX10 drives mouse spermatogonial stem cell establishment through a transcription factor signaling cascade. Cell Rep 36(3):109423
abstractText  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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