Back to Search
Start Over
Spontaneously slow-cycling subpopulations of human cells originate from activation of stress-response pathways.
- Source :
- PLoS Biology; 3/13/2019, Vol. 17 Issue 3, p1-25, 25p, 2 Charts, 5 Graphs
- Publication Year :
- 2019
-
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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 15449173
- Volume :
- 17
- Issue :
- 3
- Database :
- Complementary Index
- Journal :
- PLoS Biology
- Publication Type :
- Academic Journal
- Accession number :
- 135309148
- Full Text :
- https://doi.org/10.1371/journal.pbio.3000178