Rac mediates mouse spermatogonial stem cell homing to germline niches by regulating transmigration through the blood-testis barrier

Cell Stem Cell. 2011 Nov 4;9(5):463-75. doi: 10.1016/j.stem.2011.08.011.

Abstract

The homing ability of spermatogonial stem cells (SSCs) allows them to migrate into niches after being transplantated into infertile testes. Transplanted SSCs attach to Sertoli cells and transmigrate through the blood-testis barrier (BTB), formed by inter-Sertoli tight junctions, toward niches on the basement membrane. The most critical step is the passage through the BTB, which limits the homing efficiency to <10%. Here we demonstrated the involvement of Rac1 in SSC transmigration. Rac1-deficient SSCs did not colonize the adult testes, but they reinitiated spermatogenesis when transplanted into pup testes without a BTB. Moreover, a dominant-negative Rac1 construct not only reduced the expression of several claudin proteins, which comprise the BTB, but also increased SSC proliferation both in vitro and in vivo. Short hairpin RNA (shRNA) -mediated suppression of claudin3, which was downregulated by Rac inhibition, reduced the SSC homing efficiency. Thus, Rac1 is a critical regulator of SSC homing and proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood-Testis Barrier / cytology
  • Blood-Testis Barrier / metabolism*
  • Cell Shape
  • Cells, Cultured
  • Colony-Forming Units Assay
  • Embryo, Mammalian / cytology
  • Enzyme Activation
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Gene Deletion
  • Gene Expression Regulation
  • Male
  • Mice
  • Mice, Knockout
  • Mutation / genetics
  • Neuropeptides / genetics
  • Neuropeptides / metabolism*
  • Spermatogonia / cytology*
  • Spermatogonia / metabolism
  • Spermatogonia / transplantation
  • Stem Cell Niche*
  • Stem Cells / cytology*
  • Stem Cells / metabolism
  • Tight Junctions / metabolism
  • Transendothelial and Transepithelial Migration*
  • rac GTP-Binding Proteins / genetics
  • rac GTP-Binding Proteins / metabolism*
  • rac1 GTP-Binding Protein

Substances

  • Neuropeptides
  • Rac1 protein, mouse
  • rac GTP-Binding Proteins
  • rac1 GTP-Binding Protein