Takase Hinako M, Nusse Roeland
Department of Developmental Biology, Stanford University, Stanford, CA 94305; Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305; Department of Experimental Animal Model for Human Disease, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, Japan.
Department of Developmental Biology, Stanford University, Stanford, CA 94305; Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305;
Proc Natl Acad Sci U S A. 2016 Mar 15;113(11):E1489-97. doi: 10.1073/pnas.1601461113. Epub 2016 Feb 29.
Spermatogonial stem cells (SSCs) fuel the production of male germ cells but the mechanisms behind SSC self-renewal, proliferation, and differentiation are still poorly understood. Using the Wnt target gene Axin2 and genetic lineage-tracing experiments, we found that undifferentiated spermatogonia, comprising SSCs and transit amplifying progenitor cells, respond to Wnt/β-catenin signals. Genetic elimination of β-catenin indicates that Wnt/β-catenin signaling promotes the proliferation of these cells. Signaling is likely initiated by Wnt6, which is uniquely expressed by neighboring Sertoli cells, the only somatic cells in the seminiferous tubule that support germ cells and act as a niche for SSCs. Therefore, unlike other stem cell systems where Wnt/β-catenin signaling is implicated in self-renewal, the Wnt pathway in the testis specifically contributes to the proliferation of SSCs and progenitor cells.
精原干细胞（SSCs）驱动雄性生殖细胞的产生，但SSC自我更新、增殖和分化背后的机制仍知之甚少。通过使用Wnt靶基因Axin2和遗传谱系追踪实验，我们发现包括SSCs和过渡增殖祖细胞在内的未分化精原细胞对Wnt/β-连环蛋白信号有反应。β-连环蛋白的基因消除表明Wnt/β-连环蛋白信号促进这些细胞的增殖。信号可能由Wnt6启动，Wnt6由相邻的支持细胞独特表达，支持细胞是生精小管中唯一支持生殖细胞并作为SSCs微环境的体细胞。因此，与其他Wnt/β-连环蛋白信号参与自我更新的干细胞系统不同，睾丸中的Wnt通路专门促进SSCs和祖细胞的增殖。
