Dormant Intestinal Stem Cells Are Regulated by PTEN and Nutritional Status

Cell Reports

Hannah D. Rickner¹  Horatio Thomas¹  Manasvi S. Shah¹  Lijie Jiang¹  Luke T. Deary¹  David T. Breault¹  Danny C. Trotier¹  Diana L. Carlone¹  Dana M. Ambruzs¹  Alessio Tovaglieri¹  Robert K. Montgomery²  Camilla A. Richmond²  Bristol B. Whiles³ 

[1] Division of Endocrinology, Boston Children’s Hospital, Boston, MA 02115, USA;Division of Gastroenterology, Boston Children’s Hospital, Boston, MA 02115, USA;Harvard Stem Cell Institute, 7 Divinity Avenue, Cambridge, MA 02138, USA;

关键词: dormant;    quiescent;    intestinal stem cells;    PTEN;    fasting;    MTORC1;   

DOI  :  10.1016/j.celrep.2015.11.035

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown