Coordinate control of basal epithelial cell fate and stem cell maintenance by core EMT transcription factor Zeb1.
Coordinate control of basal epithelial cell fate and stem cell maintenance by core EMT transcription factor Zeb1.
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核心上皮间质转化转录因子Zeb1对基底上皮细胞命运和干细胞维持的协同调控
DOI：
10.1016/j.celrep.2021.110240
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发表时间：
2022-01-11
期刊：
影响因子：
8.8
通讯作者：
Dai X
中科院分区：
文献类型：
--
作者：
Han Y;Villarreal-Ponce A;Gutierrez G Jr;Nguyen Q;Sun P;Wu T;Sui B;Berx G;Brabletz T;Kessenbrock K;Zeng YA;Watanabe K;Dai X
维持基底室中未分化、长寿命且通常静止的干细胞对于多种上皮组织的稳态和再生是重要的，但是协调控制基底细胞命运和干细胞静止的分子机制是难以捉摸的。在这里，我们报告了Zeb 1，上皮细胞间质转化的核心转录诱导因子，乳腺上皮导管侧分支和基底细胞再生能力的上皮内在要求。我们的研究结果揭示了Zeb 1在促进基底细胞命运超过管腔分化中的进化保守作用。我们发现，Zeb 1损失的结果增加基底细胞增殖的代价静止和自我更新。此外，Zeb 1与雅普合作激活Axin 2表达，并且抑制Wnt信号传导部分恢复Zeb 1缺陷的基底细胞的干细胞功能。因此，Zeb 1是一种转录调节因子，维持基础细胞的命运和干细胞的静止，它的功能部分通过抑制Wnt信号。维持基底室中未分化的、长寿命的且通常静止的干细胞对于无数上皮组织的稳态和再生是重要的。Han等人报告了涉及Zeb 1的乳腺上皮内在机制，Zeb 1以其在上皮-间充质可塑性中的作用而闻名，其调节基底细胞命运和干细胞静止。
Maintenance of undifferentiated, long-lived, and often quiescent stem cells in the basal compartment is important for homeostasis and regeneration of multiple epithelial tissues, but the molecular mechanisms that coordinately control basal cell fate and stem cell quiescence are elusive. Here, we report an epithelium-intrinsic requirement for Zeb1, a core transcriptional inducer of epithelial-to-mesenchymal transition, for mammary epithelial ductal side branching and for basal cell regenerative capacity. Our findings uncover an evolutionarily conserved role of Zeb1 in promoting basal cell fate over luminal differentiation. We show that Zeb1 loss results in increased basal cell proliferation at the expense of quiescence and self-renewal. Moreover, Zeb1 cooperates with YAP to activate Axin2 expression, and inhibition of Wnt signaling partially restores stem cell function to Zeb1-deficient basal cells. Thus, Zeb1 is a transcriptional regulator that maintains both basal cell fate and stem cell quiescence, and it functions in part through suppressing Wnt signaling. Maintenance of undifferentiated, long-lived, and often quiescent stem cells in the basal compartment is important for homeostasis and regeneration of myriad epithelial tissues. Han et al. report a mammary epithelium-intrinsic mechanism involving Zeb1, known for its role in epithelial-mesenchymal plasticity, that regulates both basal cell fate and stem cell quiescence.
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影响因子：
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作者：
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