biostudies-literatureTakashima SU.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)NHLBI NIH HHSNCI NIH HHSU.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)138https://www.ebi.ac.uk/biostudies/studies/S-EPMC11697299biostudies-literatureUnknown16(1)The role of the immune system in regulating tissue stem cells remains poorly understood, as does the relationship between immune-mediated tissue damage and regeneration. Graft vs. host disease (GVHD) occurring after allogeneic bone marrow transplantation (allo-BMT) involves immune-mediated damage to the intestinal epithelium and its stem cell compartment. To assess impacts of T-cell-driven injury on distinct epithelial constituents, we have performed single cell RNA sequencing on intestinal crypts following experimental BMT. Intestinal stem cells (ISCs) from GVHD mice have exhibited global transcriptomic changes associated with a substantial Interferon-γ response and upregulation of STAT1. To determine its role in crypt function, STAT1 has been deleted within murine intestinal epithelium. Nature communicationsSTAT1 regulates immune-mediated intestinal stem cell proliferation and epithelial regeneration.PMC11697299R01 HL146338R01-HL145631R01-HL146338R01 HL145631P30 CA008748R01 HL125571R01-HL125571P30-CA008748Calafiore MFu YYChaudhary OGeiger HMazutis LHanash AMIto TRobine NSharma RArnhold VLindemans CAEgorova AChang WJansen SAKuttiyara JTakashima SIwasaki HLiu CSharrock JSantosa ESun JfalseSTAT1 regulates immune-mediated intestinal stem cell proliferation and epithelial regeneration.The role of the immune system in regulating tissue stem cells remains poorly understood, as does the relationship between immune-mediated tissue damage and regeneration. Graft vs. host disease (GVHD) occurring after allogeneic bone marrow transplantation (allo-BMT) involves immune-mediated damage to the intestinal epithelium and its stem cell compartment. To assess impacts of T-cell-driven injury on distinct epithelial constituents, we have performed single cell RNA sequencing on intestinal crypts following experimental BMT. Intestinal stem cells (ISCs) from GVHD mice have exhibited global transcriptomic changes associated with a substantial Interferon-γ response and upregulation of STAT1. To determine its role in crypt function, STAT1 has been deleted within murine intestinal epithelium. 2025-01-01T00:00:00Z2025 Jan2026-06-01T08:46:43.832Z2025-04-04T12:02:35.811ZS-EPMC116972993974693310.1038/s41467-024-55227-5