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Dormant Intestinal Stem Cells Are Regulated by PTEN and Nutritional Status. | LitMetric

Dormant Intestinal Stem Cells Are Regulated by PTEN and Nutritional Status.

Cell Rep

Division of Endocrinology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA; Harvard Stem Cell Institute, 7 Divinity Avenue, Cambridge, MA 02138, USA. Electronic address:

Published: December 2015

AI Article Synopsis

Article Abstract

The cellular and molecular mechanisms underlying adaptive changes to physiological stress within the intestinal epithelium remain poorly understood. Here, we show that PTEN, a negative regulator of the PI3K→AKT→mTORC1-signaling pathway, is an important regulator of dormant intestinal stem cells (d-ISCs). Acute nutrient deprivation leads to transient PTEN phosphorylation within d-ISCs and a corresponding increase in their number. This release of PTEN inhibition renders d-ISCs functionally poised to contribute to the regenerative response during re-feeding via cell-autonomous activation of the PI3K→AKT→mTORC1 pathway. Consistent with its role in mediating cell survival, PTEN is required for d-ISC maintenance at baseline, and intestines lacking PTEN have diminished regenerative capacity after irradiation. Our results highlight a PTEN-dependent mechanism for d-ISC maintenance and further demonstrate the role of d-ISCs in the intestinal response to stress.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4691543PMC
http://dx.doi.org/10.1016/j.celrep.2015.11.035DOI Listing

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