SHISA6 Confers Resistance to Differentiation-Promoting Wnt/?-Catenin Signaling in Mouse Spermatogenic Stem Cells.

ABSTRACT: In the seminiferous tubules of mouse testes, a population of glial cell line-derived neurotrophic factor family receptor alpha 1 (GFR?1)-positive spermatogonia harbors the stem cell functionality and supports continual spermatogenesis, likely independent of asymmetric division or definitive niche control. Here, we show that activation of Wnt/?-catenin signaling promotes spermatogonial differentiation and reduces the GFR?1⁺ cell pool. We further discovered that SHISA6 is a cell-autonomous Wnt inhibitor that is expressed in a restricted subset of GFR?1⁺ cells and confers resistance to the Wnt/?-catenin signaling. Shisa6⁺ cells appear to show stem cell-related characteristics, conjectured from the morphology and long-term fates of T (Brachyury)⁺ cells that are found largely overlapped with Shisa6⁺ cells. This study proposes a generic mechanism of stem cell regulation in a facultative (or open) niche environment, with which different levels of a cell-autonomous inhibitor (SHISA6, in this case) generates heterogeneous resistance to widely distributed differentiation-promoting extracellular signaling, such as WNTs.

SUBMITTER: Tokue M 

PROVIDER: S-EPMC5355566 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature