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. |