Cai Cheguo, Yu Qing Cissy, Jiang Weimin, Liu Wei, Song Wenqian, Yu Hua, Zhang Lei, Yang Ying, Zeng Yi Arial
The State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
The State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
Genes Dev. 2014 Oct 15;28(20):2205-18. doi: 10.1101/gad.245142.114. Epub 2014 Sep 26.
Signals from the niche play pivotal roles in regulating adult stem cell self-renewal. Previous studies indicated that the steroid hormones can expand mammary stem cells (MaSCs) in vivo. However, the facilitating local niche factors that directly contribute to the MaSC expansion remain unclear. Here we identify R-spondin1 (Rspo1) as a novel hormonal mediator in the mammary gland. Pregnancy and hormonal treatment up-regulate Rspo1 expression. Rspo1 cooperates with another hormonal mediator, Wnt4, to promote MaSC self-renewal through Wnt/β-catenin signaling. Knockdown of Rspo1 and Wnt4 simultaneously abolishes the stem cell reconstitution ability. In culture, hormonal treatment that stimulates the expression of both Rspo1 and Wnt4 can completely substitute for exogenous Wnt proteins, potently expand MaSCs, and maintain their full development potential in transplantation. Our data unveil the intriguing concept that hormones induce a collaborative local niche environment for stem cells.
来自微环境的信号在调节成体干细胞自我更新中起关键作用。先前的研究表明，类固醇激素可在体内扩增乳腺干细胞（MaSCs）。然而，直接促成MaSC扩增的局部促进性微环境因子仍不清楚。在此，我们确定R-spondin1（Rspo1）是乳腺中的一种新型激素介质。妊娠和激素治疗可上调Rspo1表达。Rspo1与另一种激素介质Wnt4协同作用，通过Wnt/β-连环蛋白信号通路促进MaSC自我更新。同时敲低Rspo1和Wnt4可消除干细胞重建能力。在培养中，刺激Rspo1和Wnt4表达的激素治疗可完全替代外源性Wnt蛋白，有力地扩增MaSCs，并在移植中维持其完全发育潜能。我们的数据揭示了一个有趣的概念，即激素为干细胞诱导出一种协同的局部微环境。
