The Homeobox Transcription Factor RHOX10 Drives Mouse Spermatogonial Stem Cell Establishment.

Cell Rep
Publication Year: 
Hye-Won Song
Anilkumar Bettegowda
Blue B Lake
Adrienne H Zhao
David Skarbrevik
Eric Babajanian
Meena Sukhwani
Eleen Y Shum
Mimi H Phan
Terra-Dawn M Plank
Marcy E Richardson
Madhuvanthi Ramaiah
Vaishnavi Sridhar
Dirk G de Rooij
Kyle E Orwig
Kun Zhang
Miles F Wilkinson
PubMed link: 
Public Summary: 
Scientific Abstract: 
The developmental origins of most adult stem cells are poorly understood. Here, we report the identification of a transcription factor-RHOX10-critical for the initial establishment of spermatogonial stem cells (SSCs). Conditional loss of the entire 33-gene X-linked homeobox gene cluster that includes Rhox10 causes progressive spermatogenic decline, a phenotype indistinguishable from that caused by loss of only Rhox10. We demonstrate that this phenotype results from dramatically reduced SSC generation. By using a battery of approaches, including single-cell-RNA sequencing (scRNA-seq) analysis, we show that Rhox10 drives SSC generation by promoting pro-spermatogonia differentiation. Rhox10 also regulates batteries of migration genes and promotes the migration of pro-spermatogonia into the SSC niche. The identification of an X-linked homeobox gene that drives the initial generation of SSCs has implications for the evolution of X-linked gene clusters and sheds light on regulatory mechanisms influencing adult stem cell generation in general.