Autor: |
Adrienne H. Zhao, Eric Babajanian, Eleen Shum, Vaishnavi Sridhar, Marcy E. Richardson, Terra-Dawn M. Plank, Hye-Won Song, Meena Sukhwani, Dirk G. de Rooij, Anilkumar Bettegowda, David Skarbrevik, Blue B. Lake, Mimi H. Phan, Kyle E. Orwig, Kun Zhang, Madhuvanthi Ramaiah, Miles F. Wilkinson |
Rok vydání: |
2015 |
Předmět: |
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Zdroj: |
Cell Reports, Vol 17, Iss 1, Pp 149-164 (2016) Cell reports, vol 17, iss 1 |
ISSN: |
2211-1247 |
Popis: |
SummaryThe 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. |
Databáze: |
OpenAIRE |
Externí odkaz: |
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