R-spondin1 is a novel hormone mediator for mammary stem cell self-renewal.
R-spondin1 is a novel hormone mediator for mammary stem cell self-renewal.
复制标题
R-spondin1 是一种用于乳腺干细胞自我更新的新型激素介质
DOI：
10.1101/gad.245142.114
复制
发表时间：
2014-10-15
影响因子：
10.5
通讯作者：
Zeng YA
中科院分区：
文献类型：
--
作者：
Cai C;Yu QC;Jiang W;Liu W;Song W;Yu H;Zhang L;Yang Y;Zeng YA
Cai等人发现Rspo 1与另一种激素介质Wnt 4合作，通过Wnt/β-catenin信号传导促进乳腺干细胞（MaSC）自我更新。刺激Rspo 1和Wnt 4表达的激素治疗可以完全替代外源Wnt蛋白，有效地扩增MaSCs，并在移植中保持其充分的发育潜力。这项研究表明，激素可以诱导干细胞的协作局部生态位环境。来自小生境的信号在调节成体干细胞自我更新中起关键作用。以往的研究表明，类固醇激素可以在体内扩增乳腺干细胞。然而，促进当地的利基因素，直接有助于MaSC的扩张仍然不清楚。在这里，我们确定R-spondin 1（Rspo 1）作为一种新的激素介质在乳腺。妊娠和激素治疗上调Rspo 1表达。Rspo 1与另一种激素介质Wnt 4合作，通过Wnt/β-catenin信号传导促进MaSC自我更新。Rspo 1和Wnt 4的敲除同时消除了干细胞的重建能力。在培养中，刺激Rspo 1和Wnt 4表达的激素治疗可以完全替代外源Wnt蛋白，有效地扩增MaSCs，并在移植中保持其充分的发育潜力。我们的数据揭示了一个有趣的概念，即激素诱导干细胞的协作局部生态位环境。
Cai et al. find that Rspo1 cooperates with another hormonal mediator, Wnt4, to promote mammary stem cell (MaSC) self-renewal through Wnt/β-catenin signaling. 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. This study shows that hormones can induce a collaborative local niche environment for stem cells. 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.