Dormant Intestinal Stem Cells Are Regulated by PTEN and Nutritional Status

作者：Richmond Camilla A; Shah Manasvi S; Deary Luke T; Trotier Danny C; Thomas Horatio; Ambruzs Dana M; Jiang Lijie; Whiles Bristol B; Rickner Hannah D; Montgomery Robert K; Tovaglieri Alessio; Carlone Diana L; Breault David T^*

来源：Cell Reports, 2015, 13(11): 2403-2411.

DOI：10.1016/j.celrep.2015.11.035

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.

• 出版日期2015-12-22