c-Kit+ cells that intercalate with crypt Lgr5+ cells are distinctively multipotent in colonic epithelium renewal and repair by Qing Xu & Yuting Zeng & Lan Jiang & Yongjie Zhou & Zhenru Wu & Shiyu Liu & Ruoting Men & Shujun Li & Jiayin Yang & Wei Huang & Yujun Shi instant download

c-Kit+ cells that intercalate with crypt Lgr5+ cells are distinctively multipotent in colonic epithelium renewal and repair by Qing Xu & Yuting Zeng & Lan Jiang & Yongjie Zhou & Zhenru Wu & Shiyu Liu & Ruoting Men & Shujun Li & Jiayin Yang & Wei Huang & Yujun Shi instant download

The colonic crypts are principally composed by Lgr5+ stem cells and deep crypt secretory (DCS) cells. c-Kit-expressing cells markDCS 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+ cells1234567890();,:are a heterogeneous entity and possess stemness potency to differentiate into the entire spectrum of epithelial cells and renew thehomeostatic colon. Intriguingly, c-Kit+ cells play a pivotal role in epithelium repair in mouse models of colitis when contemporaryLgr5+ cells are insufficient or absent. Depletion of c-Kit+ cells or inhibition of SCF/c-Kit signaling worsens, while supplementation ofSCF alleviates colonic epithelium injury during colitis. Our findings unravel the fate and function of c-Kit+ cells in homeostatic colonand recovery during colonic epithelium injury which has translational implications for human inflammatory bowel diseases.Cell Death & Differentiation (2025) 32:1244–1258;