Anal skin-like epithelium mediates colonic wound healing [article]

Cambrian Y. Liu, Nandini Girish, Marie L. Gomez, Philip E. Dube, M. Kay Washington, Benjamin D. Simons, D. Brent Polk
2021 bioRxiv   pre-print
Intestinal epithelial wound healing, which is essential for health, is compromised and represents a therapeutic target in inflammatory bowel disease (IBD). While studies have elucidated important subpopulations of intestinal epithelial cells in repair, these have yet to translate to therapies. Here, in mouse models of acute colitis, we demonstrate a distinct and essential source of wound-healing cells that re-epithelialize the distal colon. Using 3-d imaging, lineage tracing, and single-cell
more » ... nscriptomics, we show that neighboring skin-like (squamous) cells of the anus rapidly migrate into the injured colon and establish a permanent epithelium of crypt-like morphology. These squamous cells derive from a small unique transition zone, at the boundary of colonic and anal epithelium, that resists colitis. The cells of this zone have a pre-loaded program of colonic differentiation and further upregulate key aspects of colonic epithelium during repair. Thus, heterologous cell-types at tissue junctions represent unique reserve cells capable of repair and plasticity.
doi:10.1101/2021.06.02.446836 fatcat:3bz4yymv2ze2hiurjrpria77ne