Regulation of spermatogonial stem cell self-renewal in mammals

Annu Rev Cell Dev Biol. 2008;24:263-86. doi: 10.1146/annurev.cellbio.24.110707.175355.


Mammalian spermatogenesis is a classic adult stem cell-dependent process, supported by self-renewal and differentiation of spermatogonial stem cells (SSCs). Studying SSCs provides a model to better understand adult stem cell biology, and deciphering the mechanisms that control SSC functions may lead to treatment of male infertility and an understanding of the etiology of testicular germ cell tumor formation. Self-renewal of rodent SSCs is greatly influenced by the niche factor glial cell line-derived neurotrophic factor (GDNF). In mouse SSCs, GDNF activation upregulates expression of the transcription factor-encoding genes bcl6b, etv5, and lhx1, which influence SSC self-renewal. Additionally, the non-GDNF-stimulated transcription factors Plzf and Taf4b have been implicated in regulating SSC functions. Together, these molecules are part of a robust gene network controlling SSC fate decisions that may parallel the regulatory networks in other adult stem cell populations.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation / physiology
  • Glial Cell Line-Derived Neurotrophic Factor / metabolism
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Kruppel-Like Transcription Factors / genetics
  • Kruppel-Like Transcription Factors / metabolism
  • Male
  • Mammals*
  • Phenotype
  • Pluripotent Stem Cells / cytology
  • Pluripotent Stem Cells / physiology
  • Spermatogenesis / physiology*
  • Spermatogonia / cytology*
  • Stem Cell Transplantation
  • Stem Cells / cytology
  • Stem Cells / physiology*
  • TATA-Binding Protein Associated Factors / genetics
  • TATA-Binding Protein Associated Factors / metabolism
  • Testis / anatomy & histology
  • Transcription Factor TFIID / genetics
  • Transcription Factor TFIID / metabolism


  • Glial Cell Line-Derived Neurotrophic Factor
  • Intercellular Signaling Peptides and Proteins
  • Kruppel-Like Transcription Factors
  • TATA-Binding Protein Associated Factors
  • Taf4b protein, mouse
  • Transcription Factor TFIID