Brat promotes stem cell differentiation via control of a bistable switch that restricts BMP signaling.
Brat promotes stem cell differentiation via control of a bistable switch that restricts BMP signaling.
复制标题
小子通过控制限制BMP信号传导的双态开关来促进干细胞分化。
DOI：
10.1016/j.devcel.2010.11.019
复制
发表时间：
2011-01-18
影响因子：
11.8
通讯作者：
Ashe, Hilary L.
中科院分区：
文献类型：
--
作者：
Harris, Robin E.;Pargett, Michael;Sutcliffe, Catherine;Umulis, David;Ashe, Hilary L.
果蝇卵巢生殖系干细胞(GSCs)由DPP信号和Pum和Nanos翻译抑制因子维持。一旦分裂，DPP信号被熄灭，一个子细胞中的NOS被下调，导致它切换到一个分化的成囊细胞(CB)。然而，Pum-Nos的下游效应尚不清楚，CBS如何失去对DPP的反应性也不清楚。在这里，我们确定脑瘤(BRAT)是一种有效的分化因子和Pum-Nos调控的靶点。Brat被Pum-No排除在GSC之外，但在CBS中与Pum一起作用于翻译抑制不同的靶标，包括Mad和dMyc mRNAs。同时调节这两个靶点会降低细胞对DPP信号的反应性，迫使细胞对自我更新信号变得不耐受。数学模型阐明了BRAT介导的系统中细胞命运的双稳性，揭示了BRAT如何将细胞外DPP调节与细胞内解释结合起来对GSC数量进行自动调节。►Pumilio和Nano翻译抑制生殖系干细胞中的Brat mRNAs►Brat通过限制DPP信号和细胞生长促进分化►BRAT与Pumilio共同作用抑制Mad和dMyc mRNAs的翻译►模拟表明BRAT创建双稳并提供强大的细胞命运控制
Drosophila ovarian germline stem cells (GSCs) are maintained by Dpp signaling and the Pumilio (Pum) and Nanos (Nos) translational repressors. Upon division, Dpp signaling is extinguished, and Nos is downregulated in one daughter cell, causing it to switch to a differentiating cystoblast (CB). However, downstream effectors of Pum-Nos remain unknown, and how CBs lose their responsiveness to Dpp is unclear. Here, we identify Brain Tumor (Brat) as a potent differentiation factor and target of Pum-Nos regulation. Brat is excluded from GSCs by Pum-Nos but functions with Pum in CBs to translationally repress distinct targets, including the Mad and dMyc mRNAs. Regulation of both targets simultaneously lowers cellular responsiveness to Dpp signaling, forcing the cell to become refractory to the self-renewal signal. Mathematical modeling elucidates bistability of cell fate in the Brat-mediated system, revealing how autoregulation of GSC number can arise from Brat coupling extracellular Dpp regulation to intracellular interpretation. ► Pumilio and Nanos translationally repress brat mRNA in germline stem cells ► Brat promotes differentiation by limiting Dpp signaling and cellular growth ► Brat acts with Pumilio to repress translation of the Mad and dMyc mRNAs ► Modeling shows Brat creates bistability and provides robust cell-fate control
登录
查看更多内容
影响因子：
9.2
作者：
Jin, Zhigang;Xie, Ting
通讯作者：
Xie, Ting
影响因子：
21.3
作者：
Grewal, SS;Li, L;Edgar, BA
通讯作者：
Edgar, BA
影响因子：
8
作者：
Arama, E;Dickman, D;Lev, Z
通讯作者：
Lev, Z
影响因子：
3.3
作者：
Glasscock, E;Singhania, A;Tanouye, MA
通讯作者：
Tanouye, MA
影响因子：
9.2
作者：
Cho, Park F.;Gamberi, Chiara;Sonenberg, Nahum
通讯作者：
Sonenberg, Nahum