The RNA-binding protein NANOS2 is required to maintain murine spermatogonial stem cells

Science. 2009 Sep 11;325(5946):1394-8. doi: 10.1126/science.1172645.

Abstract

Stem cells give rise to differentiated cell types but also preserve their undifferentiated state through cell self-renewal. With the use of transgenic mice, we found that the RNA-binding protein NANOS2 is essential for maintaining spermatogonial stem cells. Lineage-tracing analyses revealed that undifferentiated spermatogonia expressing Nanos2 self-renew and generate the entire spermatogenic cell lineage. Conditional disruption of postnatal Nanos2 depleted spermatogonial stem cell reserves, whereas mouse testes in which Nanos2 had been overexpressed accumulated spermatogonia with undifferentiated, stem cell-like properties. Thus, NANOS2 is a key stem cell regulator that is expressed in self-renewing spermatogonial stem cells and maintains the stem cell state during murine spermatogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Differentiation
  • Cell Lineage
  • Gene Knockout Techniques
  • Glial Cell Line-Derived Neurotrophic Factor Receptors / metabolism
  • Kruppel-Like Transcription Factors / metabolism
  • Male
  • Mice
  • Mice, Transgenic
  • Nerve Tissue Proteins / metabolism
  • Promyelocytic Leukemia Zinc Finger Protein
  • RNA-Binding Proteins / metabolism
  • Spermatogenesis*
  • Spermatogonia / cytology*
  • Spermatogonia / metabolism
  • Stem Cells / cytology*
  • Stem Cells / metabolism
  • Testis / cytology
  • Testis / metabolism
  • Zinc Fingers

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Carrier Proteins
  • Gfra1 protein, mouse
  • Glial Cell Line-Derived Neurotrophic Factor Receptors
  • Kruppel-Like Transcription Factors
  • Nanos2 protein, mouse
  • Nanos3 protein, mouse
  • Nerve Tissue Proteins
  • Neurog3 protein, mouse
  • Promyelocytic Leukemia Zinc Finger Protein
  • RNA-Binding Proteins
  • Zbtb16 protein, mouse