Department of Molecular Genetics, Graduate School of Medicine, Kyoto University, 606-8501 Kyoto, Japan.
Agency for Medical Research and Development-Core Research for Evolutional Science and Technology (AMED-CREST), AMED, Chiyodaku, 100-0004 Tokyo, Japan.
Proc Natl Acad Sci U S A. 2020 Apr 7;117(14):7837-7844. doi: 10.1073/pnas.1914963117. Epub 2020 Mar 30.
The blood-testis barrier (BTB) is thought to be indispensable for spermatogenesis because it creates a special environment for meiosis and protects haploid cells from the immune system. The BTB divides the seminiferous tubules into the adluminal and basal compartments. Spermatogonial stem cells (SSCs) have a unique ability to transmigrate from the adluminal compartment to the basal compartment through the BTB upon transplantation into the seminiferous tubule. Here, we analyzed the role of , a major component of the BTB, in spermatogenesis using spermatogonial transplantation. -deficient mice are infertile due to the cessation of spermatogenesis at the spermatocyte stage. -deficient SSCs failed to colonize wild-type testes efficiently, and -deficient SSCs that underwent double depletion of and showed minimal colonization, suggesting that claudins on SSCs are necessary for transmigration. However, -deficient Sertoli cells increased SSC homing efficiency by >3-fold, suggesting that CLDN11 in Sertoli cells inhibits transmigration of SSCs through the BTB. In contrast to endogenous SSCs in intact -deficient testes, those from WT or -deficient testes regenerated sperm in -deficient testes. The success of this autologous transplantation appears to depend on removal of endogenous germ cells for recipient preparation, which reprogrammed claudin expression patterns in Sertoli cells. Consistent with this idea, in vivo depletion of / regenerated endogenous spermatogenesis in -deficient mice. Thus, coordinated claudin expression in both SSCs and Sertoli cells expression is necessary for SSC homing and regeneration of spermatogenesis, and autologous stem cell transplantation can rescue congenital defects of a self-renewing tissue.
血睾屏障（BTB）被认为对于精子发生是必不可少的，因为它为减数分裂创造了一个特殊的环境，并保护了单倍体细胞免受免疫系统的侵害。BTB 将生精小管分隔为管腔和基底隔室。精原干细胞（SSC）具有独特的能力，可在移植到生精小管后通过 BTB 从管腔隔室迁移到基底隔室。在这里，我们使用精原干细胞移植分析了 BTB 的主要成分 Claudin11 在精子发生中的作用。 Claudin11 缺陷型小鼠由于精母细胞阶段的精子发生停止而不育。 Claudin11 缺陷型 SSC 未能有效地定植野生型睾丸，并且经历 Claudin11 和 Claudin14 双重耗竭的 Claudin11 缺陷型 SSC 显示出最小的定植，表明 SSC 上的 Claudins 对于迁移是必要的。然而，Claudin11 缺陷型 Sertoli 细胞通过增加 SSC 归巢效率超过 3 倍，表明 Sertoli 细胞中的 Claudin11 抑制 SSC 通过 BTB 的迁移。与完整的 Claudin11 缺陷型睾丸中的内源性 SSC 相反，来自 WT 或 Claudin11 缺陷型睾丸的 SSC 在 Claudin11 缺陷型睾丸中再生精子。这种自体移植的成功似乎取决于受体准备过程中对内源性生殖细胞的去除，这使 Sertoli 细胞中的 Claudin 表达模式重新编程。与这一观点一致，体内 Claudin11 和 Claudin14 的耗竭在 Claudin11 缺陷型小鼠中再生了内源性精子发生。因此，SSC 和 Sertoli 细胞表达中的 Claudin 表达的协调对于 SSC 归巢和精子发生的再生是必要的，并且自体干细胞移植可以挽救自我更新组织的先天性缺陷。
