Department of Molecular Genetics, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
Cell Stem Cell. 2011 Nov 4;9(5):463-75. doi: 10.1016/j.stem.2011.08.011.
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.
精原干细胞（SSCs）的归巢能力使其在移植到不育睾丸后能够迁移到巢中。移植的 SSCs 附着在支持细胞上，并穿过由支持细胞紧密连接形成的血睾屏障（BTB），向基底膜上的巢迁移。最关键的步骤是穿过 BTB，这将归巢效率限制在<10%。在这里，我们证明了 Rac1 在 SSC 迁移中的参与。Rac1 缺陷的 SSCs 不会定植成年睾丸，但当移植到没有 BTB 的幼鼠睾丸时，它们会重新开始精子发生。此外，显性失活 Rac1 构建体不仅降低了构成 BTB 的几种紧密连接蛋白的表达，而且还增加了体外和体内 SSC 的增殖。短发夹 RNA（shRNA）介导的 Claudin3 抑制，其表达被 Rac 抑制下调，降低了 SSC 的归巢效率。因此，Rac1 是 SSC 归巢和增殖的关键调节剂。
