Mucosal Single-Cell Profiling of Crohn's-Like Disease of the Pouch Reveals Unique Pathogenesis and Therapeutic Targets

The pathophysiology of Crohn’s-like disease of the pouch (CDP) that develops after restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC) is unknown. We examined mucosal cells from patients with and without CDP using single cell analyses. Endoscopic samples were collected from the pouch body and pre-pouch ileum (refer to as “pouch/ileum”) of 50 patients with an IPAA. Single-cell RNA sequencing (scRNA-seq) was performed on pouch/ileal tissues of patients with normal pouch/ileum and CDP. Mass cytometry was performed on mucosal immune cells from patients with normal pouch/ileum, CDP, pouchitis, as well as those with familial adenomatous polyposis (FAP) after pouch formation. Findings were independently validated using immunohistochemistry. *************************************************************** Submitter states that missing raw files are due to patient privacy concerns. ***************************************************************