An epigenetic basis for sustained inflammatory epithelial progenitor cell states in Crohn's disease

Defining consequential differences in intestinal epithelial stem cells in healthy humans versus those with inflammatory bowel disease (Crohn's disease (CD) and ulcerative colitis) is essential for the development of therapies to restore the epithelial barrier and maintain its fidelity post-injury. Our study objective was to define transcriptomic, epigenomic, and functional divergence between healthy and CD epithelium. Overall design: We used single cell RNA sequencing and single nuclei ATAC-sequencing (n= 27 CD, 26 control) to evaluate transcriptomic and epigenomic differences in non-inflamed CD epithelium. Matched patient organoids from the same specimens were used to investigate durable epithelial-intrinsic changes at transcriptional and functional levels. This submission contains scRNA-Seq submission.