Epigenetic changes from ATAC-seq of intestine stem cells from mice with graft-versus-host disease

Intestinal stem cells (ISC) encounter inflammatory insults in immune mediated gastro-intestinal (GI) diseases. It remains unknown whether, and how, they adapt, and if the adaptation leaves scars on the ISCs that affects their subsequent regeneration capacity. We investigated the consequences of inflammation on Lgr5+ISCs in well-defined clinically relevant models of gastro-intestinal acute graft-versus-host disease (GI GVHD). Utilizing single cell transcriptomics, organoid, metabolic, epigenomic and in vivo models we found that Lgr5+ISCs undergo metabolic changes that lead to accumulation of succinate, which reprograms its epigenome. We performed transposase-accessible chromatin sequencing (ATAC-seq) in sorted Lgr5+ISCs harvested from the BALB/c?B6-GFP-Lgr5 model of GVHD. Overall design: Fifty thousand Lgr5+ISCs were sorted by FACS from Allo- and Syn-recipients seven days following bone marrow transplantation (BMT) and analyzed by ATAC-seq