Gene expression profile at single cell level 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 GHD). 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. Single cells were isolated from small intestine crypts from Allo (BALB/c→C57BL/6) or Syn (C57BL/6→C57BL/6) transplant 7 days after bone marrow transplantation (BMT) and analyzed using scRNA-seq. Single cells were isolated from small intestine crypts from Allo (BALB/c→C57BL/6) or Syn (C57BL/6→C57BL/6) transplant 7 days after bone marrow transplantation (BMT) and analyzed using scRNA-seq.