Inflammation-induced epigenetic imprinting regulates intestinal stem cells.

ABSTRACT: It remains unknown whether and how intestinal stem cells (ISCs) adapt to inflammatory exposure and whether the adaptation leaves scars that will affect their subsequent regeneration. We investigated the consequences of inflammation on Lgr5⁺ ISCs in well-defined clinically relevant models of acute gastrointestinal graft-versus-host disease (GI GVHD). Utilizing single-cell transcriptomics, as well as organoid, metabolic, epigenomic, and in vivo models, we found that Lgr5⁺ ISCs undergo metabolic changes that lead to the accumulation of succinate, which reprograms their epigenome. These changes reduced the ability of ISCs to differentiate and regenerate ex vivo in serial organoid cultures and also in vivo following serial transplantation. Furthermore, ISCs demonstrated a

SUBMITTER: Zhao D 

PROVIDER: S-EPMC11963838 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature