SHISA6 Confers Resistance to Differentiation-Promoting Wnt/β-Catenin Signaling in Mouse Spermatogenic Stem Cells.
SHISA6 Confers Resistance to Differentiation-Promoting Wnt/β-Catenin Signaling in Mouse Spermatogenic Stem Cells.
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DOI：
10.1016/j.stemcr.2017.01.006
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发表时间：
2017-03-14
影响因子：
5.9
通讯作者：
Yoshida S
中科院分区：
文献类型：
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作者：
Tokue M;Ikami K;Mizuno S;Takagi C;Miyagi A;Takada R;Noda C;Kitadate Y;Hara K;Mizuguchi H;Sato T;Taketo MM;Sugiyama F;Ogawa T;Kobayashi S;Ueno N;Takahashi S;Takada S;Yoshida S
在小鼠睾丸生精小管中，胶质细胞源性神经营养因子家族受体α 1（GFRα1）阳性精原细胞群体具有干细胞功能，并支持持续的精子发生，可能独立于不对称分裂或确定的生态位控制。在这里，我们发现Wnt/β-catenin信号的激活促进精原细胞分化并减少GFRα1+细胞池。我们进一步发现SHISA 6是一种细胞自主Wnt抑制剂，在GFRα1+细胞的有限亚群中表达，并赋予对Wnt/β-连环蛋白信号传导的抗性。Shisa 6+细胞似乎显示出干细胞相关的特征，这是从T（Brachyury）+细胞的形态和长期命运证实的，T（Brachyury）+细胞被发现与Shisa 6+细胞在很大程度上重叠。这项研究提出了兼性（或开放）生态位环境中干细胞调节的一般机制，不同水平的细胞自主抑制剂（在这种情况下为SHISA 6）对广泛分布的促进分化的细胞外信号传导（例如WNT）产生异质性抗性。Wnt/β-catenin信号促进GFRα1+精原细胞的分化SHISA 6是在GFRα1+细胞亚群中表达的细胞自主性Wnt抑制剂SHISA 6赋予对Wnt/β-catenin信号诱导的分化的抗性SHISA 6+精原细胞显示干细胞相关特性在小鼠睾丸生精小管中，Yoshida及其同事质疑精子干细胞如何响应均匀分布的细胞外信号而遵循不同的命运（分化或自我更新）。他们表明，Shisa 6（一种细胞自主Wnt抑制剂）的异质性表达赋予了对均匀分布的分化促进Wnt信号传导的抗性。这可能是通用的干细胞调节在兼性生态位。
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. 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.