Kidney collecting duct cell type composition is regulated by Notch signaling via modulation of mTORC1 activity (RNA-Seq).

Notch signaling, a regulator of cell fate selection, ensures urine concentrating capacity in adult organisms by preventing water reabsorbing principal cell types in the kidney collecting duct segments from converting into mitochondria rich intercalated cell types.

Here we identify that Hes1, a target of Notch signaling, allows for the maintenance of functionally different epithelial cell types with differing metabolic states within the same microenvironment by regulating mechanistic target of rapamycin complex 1 (mTORC1) activity. Hes1 directly represses mTOR pathway components, such as Irs1, and suppresses mTORC1 activity in principal cells. Increasing mTORC1 activity in mature principal cells is sufficient to initiate the acquisition of intercalated cell type properties.