A Quiescent Bcl11b High Stem Cell Population Is Required for Maintenance of the Mammary Gland.
A Quiescent Bcl11b High Stem Cell Population Is Required for Maintenance of the Mammary Gland.
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DOI：
10.1016/j.stem.2016.11.007
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发表时间：
2017-02-02
期刊：
影响因子：
23.9
通讯作者：
Clarke MF
中科院分区：
文献类型：
--
作者：
Cai S;Kalisky T;Sahoo D;Dalerba P;Feng W;Lin Y;Qian D;Kong A;Yu J;Wang F;Chen EY;Scheeren FA;Kuo AH;Sikandar SS;Hisamori S;van Weele LJ;Heiser D;Sim S;Lam J;Quake S;Clarke MF
许多组织中的干细胞通过进入静止状态来维持自身，以避免基因组损伤并防止过度增殖引起的耗竭。在乳腺中，静止上皮干细胞的身份和特征尚不清楚。在这里，我们确定了一个静止的乳腺上皮细胞群表达高水平的Bcl 11b和位于管腔和基底细胞之间的界面。bcl 11bhigh细胞富含可以在二次移植中再生乳腺的细胞。Bcl 11b的缺失导致导管上皮依赖Cdkn 2a的耗竭和上皮细胞再生能力的丧失。功能获得和丧失的研究表明，Bcl 11 b诱导细胞进入细胞周期的G 0期，并变得静止。两者合计，这些结果表明，Bcl 11 b作为一个中央的内在调节乳腺上皮干细胞的静止和衰竭，是必要的长期维护乳腺。Cai等人（2016）描述了一种由Bcl 11b标记的静止乳腺干细胞群，位于支持乳腺再生的腔-基底界面。bcl 11b通过诱导促进休眠状态的细胞周期调节剂来维持这一群体。
Stem cells in many tissues sustain themselves by entering a quiescent state to avoid genomic insults and to prevent exhaustion caused by excessive proliferation. In the mammary gland, the identity and characteristics of quiescent epithelial stem cells are not clear. Here, we identify a quiescent mammary epithelial cell population expressing high levels of Bcl11b and located at the interface between luminal and basal cells. Bcl11bhigh cells are enriched for cells that can regenerate mammary glands in secondary transplants. Loss of Bcl11b leads to a Cdkn2a-dpendent exhaustion of ductal epithelium and loss of epithelial cell regenerative capacity. Gain and loss of function studies show that Bcl11b induces cells to enter the G0 phase of the cell cycle and become quiescent. Taken together, these results suggest that Bcl11b acts as a central intrinsic regulator of mammary epithelial stem cell quiescence and exhaustion, and is necessary for long-term maintenance of the mammary gland. Cai et al. (2016) describe a quiescent mammary stem cell population labeled by Bcl11b and located at the luminal-basal interface that supports mammary gland regeneration. Bcl11b sustains this population by inducing cell cycle regulators that promote the dormant state.