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Abstract
The intestinal epithelium renews rapidly through tightly regulated stem cell activity within the crypt niche. The adhesion molecule CD166, a colorectal cancer stem cell marker, has an unclear role in normal intestine. We found CD166 expression localized to Lgr5-positive stem/progenitor cells and Paneth cells, suggesting a niche-regulatory function. CD166‑null mice showed impaired proliferation, Wnt signaling, migration, reduced stem cell numbers, and smaller crypts, as well as delayed recovery after radiation injury. These findings identify CD166 as a key regulator of intestinal stem cell homeostasis with implications for epithelial regeneration and cancer.