期刊
DEVELOPMENTAL CELL
卷 40, 期 6, 页码 537-+出版社
CELL PRESS
DOI: 10.1016/j.devcel.2017.02.022
关键词
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资金
- National Natural Science Foundation of China [31471372]
- Peking-Tsinghua Center for Life Sciences
Asymmetric stem cell division establishes an initial difference between a stem cell and its differentiating sibling, critical for maintaining homeostasis and preventing carcinogenesis. Yet the mechanisms that consolidate and lock in such initial fate bias remain obscure. Here, we use Drosophila neuroblasts to demonstrate that the super elongation complex (SEC) acts as an intrinsic amplifier to drive cell fate commitment. SEC is highly expressed in neuroblasts, where it promotes self-renewal by physically associating with Notch transcription activation complex and enhancing HES (hairy and E(spl)) transcription. HES in turn upregulates SEC activity, forming an unexpected self-reinforcing feedback loop with SEC. SEC inactivation leads to neuroblast loss, whereas its forced activation results in neural progenitor dedifferentiation and tumorigenesis. Our studies unveil an SEC-mediated intracellular amplifier mechanism in ensuring robustness and precision in stem cell fate commitment and providemechanistic explanation for the highly frequent association of SEC overactivation with human cancers.
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