c-Kit cells that intercalate with crypt Lgr5 cells are distinctively multipotent in colonic epithelium renewal and repair.

The colonic crypts are principally composed by Lgr5 stem cells and deep crypt secretory (DCS) cells. c-Kit-expressing cells mark DCS cells and supply Wnt3, EGF, and Notch signals to support their neighboring crypt bottom-intermingled Lgr5 cells. However, the role of c-Kit cells beyond supporting Lgr5 cells in colonic epithelium remains unexplored. Here, we identify that c-Kit cells are a heterogeneous entity and possess stemness potency to differentiate into the entire spectrum of epithelial cells and renew the homeostatic colon. Intriguingly, c-Kit cells play a pivotal role in epithelium repair in mouse models of colitis when contemporary Lgr5 cells are insufficient or absent. Depletion of c-Kit cells or inhibition of SCF/c-Kit signaling worsens, while supplementation of SCF alleviates colonic epithelium injury during colitis. Our findings unravel the fate and function of c-Kit cells in homeostatic colon and recovery during colonic epithelium injury which has translational implications for human inflammatory bowel diseases.