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

In the seminiferous tubules of mouse testes, a population of glial cell line-derived neurotrophic factor family receptor alpha 1 (GFRα1)-positive spermatogonia harbors the stem cell functionality and supports continual spermatogenesis, likely independent of asymmetric division or definitive niche co...

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Veröffentlicht in:Stem cell reports 2017-03, Vol.8 (3), p.561-575
Hauptverfasser: Tokue, Moe, Ikami, Kanako, Mizuno, Seiya, Takagi, Chiyo, Miyagi, Asuka, Takada, Ritsuko, Noda, Chiyo, Kitadate, Yu, Hara, Kenshiro, Mizuguchi, Hiroko, Sato, Takuya, Taketo, Makoto Mark, Sugiyama, Fumihiro, Ogawa, Takehiko, Kobayashi, Satoru, Ueno, Naoto, Takahashi, Satoru, Takada, Shinji, Yoshida, Shosei
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Sprache:eng
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Zusammenfassung:In the seminiferous tubules of mouse testes, a population of glial cell line-derived neurotrophic factor family receptor alpha 1 (GFRα1)-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/β-catenin signaling promotes spermatogonial differentiation and reduces the GFRα1+ cell pool. We further discovered that SHISA6 is a cell-autonomous Wnt inhibitor that is expressed in a restricted subset of GFRα1+ cells and confers resistance to the Wnt/β-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. [Display omitted] •Wnt/β-catenin signaling promotes the differentiation of GFRα1+ spermatogonia•SHISA6 is a cell-autonomous Wnt inhibitor expressed in subset GFRα1+ cells•SHISA6 confers resistance to differentiation induction by Wnt/β-catenin signaling•SHISA6+ spermatogonia show stem cell-related properties In mouse testicular seminiferous tubules, Yoshida and colleagues questioned how sperm stem cells follow different fates (to differentiate or to self-renew) in response to homogeneously distributed extracellular signals. They showed that heterogeneous expression of Shisa6, a cell-autonomous Wnt inhibitor, confers resistance to homogeneously distributed differentiation-promoting Wnt signaling. This may be generic for stem cell regulation in a facultative niche.
ISSN:2213-6711
2213-6711
DOI:10.1016/j.stemcr.2017.01.006