[PDF][PDF] Dormant intestinal stem cells are regulated by PTEN and nutritional status

CA Richmond, MS Shah, LT Deary, DC Trotier… - Cell reports, 2015 - cell.com
CA Richmond, MS Shah, LT Deary, DC Trotier, H Thomas, DM Ambruzs, L Jiang, BB Whiles
Cell reports, 2015cell.com
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 …
Summary
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.
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