The Homeobox Transcription Factor RHOX10 Drives Mouse Spermatogonial Stem Cell Establishment

Cell Rep. 2016 Sep 27;17(1):149-164. doi: 10.1016/j.celrep.2016.08.090.


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.

Keywords: Rhox; germ cell; germ line stem cell; gonocytes; homeobox; prospermatogonia; spermatogenesis; spermatogonia; spermatogonial stem cells; transcription factor.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult Germline Stem Cells / cytology
  • Adult Germline Stem Cells / metabolism*
  • Animals
  • Gene Expression Regulation, Developmental*
  • Genes, Developmental
  • Genes, X-Linked*
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism
  • Male
  • Mice
  • Mice, Knockout
  • Multigene Family
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Sequence Analysis, RNA
  • Single-Cell Analysis
  • Spermatogenesis / genetics*
  • Spermatogonia / cytology
  • Spermatogonia / metabolism*


  • Homeodomain Proteins
  • Protein Isoforms
  • Rhox10 protein, mouse