The Homeobox Transcription Factor RHOX10 Drives Mouse Spermatogonial Stem Cell Establishment

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

doi:10.1016/j.celrep.2016.08.090

Cell Reports (Sep 2016)

The Homeobox Transcription Factor RHOX10 Drives Mouse Spermatogonial Stem Cell Establishment

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

Affiliations

Hye-Won Song: School of Medicine, Department of Reproductive Medicine, University of California at San Diego, La Jolla, CA 92093, USA
Anilkumar Bettegowda: School of Medicine, Department of Reproductive Medicine, University of California at San Diego, La Jolla, CA 92093, USA
Blue B. Lake: Department of Bioengineering, University of California at San Diego, La Jolla, CA 92093, USA
Adrienne H. Zhao: School of Medicine, Department of Reproductive Medicine, University of California at San Diego, La Jolla, CA 92093, USA
David Skarbrevik: School of Medicine, Department of Reproductive Medicine, University of California at San Diego, La Jolla, CA 92093, USA
Eric Babajanian: School of Medicine, Department of Reproductive Medicine, University of California at San Diego, La Jolla, CA 92093, USA
Meena Sukhwani: Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh School of Medicine, Magee-Womens Research Institute, Pittsburgh, PA 15213, USA
Eleen Y. Shum: School of Medicine, Department of Reproductive Medicine, University of California at San Diego, La Jolla, CA 92093, USA
Mimi H. Phan: School of Medicine, Department of Reproductive Medicine, University of California at San Diego, La Jolla, CA 92093, USA
Terra-Dawn M. Plank: School of Medicine, Department of Reproductive Medicine, University of California at San Diego, La Jolla, CA 92093, USA
Marcy E. Richardson: School of Medicine, Department of Reproductive Medicine, University of California at San Diego, La Jolla, CA 92093, USA
Madhuvanthi Ramaiah: School of Medicine, Department of Reproductive Medicine, University of California at San Diego, La Jolla, CA 92093, USA
Vaishnavi Sridhar: School of Medicine, Department of Reproductive Medicine, University of California at San Diego, La Jolla, CA 92093, USA
Dirk G. de Rooij: Reproductive Biology Group, Division of Developmental Biology, Faculty of Science, Department of Biology, Utrecht University, 3584 CH Utrecht, the Netherlands
Kyle E. Orwig: Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh School of Medicine, Magee-Womens Research Institute, Pittsburgh, PA 15213, USA
Kun Zhang: Department of Bioengineering, University of California at San Diego, La Jolla, CA 92093, USA
Miles F. Wilkinson: School of Medicine, Department of Reproductive Medicine, University of California at San Diego, La Jolla, CA 92093, USA

DOI: https://doi.org/10.1016/j.celrep.2016.08.090
Journal volume & issue: Vol. 17, no. 1
pp. 149 – 164

Abstract

Read online

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.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

About the journal

Abstract

Keywords