Spontaneously slow-cycling subpopulations of human cells originate from activation of stress-response pathways.
PLoS Biol
; 17(3): e3000178, 2019 03.
Article
in En
| MEDLINE
| ID: mdl-30865623
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Signal Transduction
/
Cell Survival
/
Neoplasms
Limits:
Humans
Language:
En
Journal:
PLoS Biol
Journal subject:
BIOLOGIA
Year:
2019
Type:
Article
Affiliation country:
United States