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Spontaneously slow-cycling subpopulations of human cells originate from activation of stress-response pathways.


ABSTRACT: Slow-cycling subpopulations exist in bacteria, yeast, and mammalian systems. In the case of cancer, slow-cycling subpopulations have been proposed to give rise to drug resistance. However, the origin of slow-cycling human cells is poorly studied, in large part due to lack of markers to identify these rare cells. Slow-cycling cells pass through a noncycling period marked by low CDK2 activity and high p21 levels. Here, we use this knowledge to isolate these naturally slow-cycling cells from a heterogeneous population and perform RNA sequencing to delineate the transcriptome underlying the slow-cycling state. We show that cellular stress responses-the p53 transcriptional response and the integrated stress response (ISR)-are the most salient causes of spontaneous entry into the slow-cycling state. Finally, we show that cells' ability to enter the slow-cycling state enhances their survival in stressful conditions. Thus, the slow-cycling state is hardwired to stress responses to promote cellular survival in unpredictable environments.

SUBMITTER: Min M 

PROVIDER: S-EPMC6433297 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Spontaneously slow-cycling subpopulations of human cells originate from activation of stress-response pathways.

Min Mingwei M   Spencer Sabrina L SL  

PLoS biology 20190313 3


Slow-cycling subpopulations exist in bacteria, yeast, and mammalian systems. In the case of cancer, slow-cycling subpopulations have been proposed to give rise to drug resistance. However, the origin of slow-cycling human cells is poorly studied, in large part due to lack of markers to identify these rare cells. Slow-cycling cells pass through a noncycling period marked by low CDK2 activity and high p21 levels. Here, we use this knowledge to isolate these naturally slow-cycling cells from a hete  ...[more]

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