biostudies-literatureBauer-Rowe KENIH National Institute of General Medical SciencesNIDCR NIH HHSNational Institutes of Health Office of Research Infrastructure ProgramsSarnoff Cardiovascular Research FoundationNational Institutes of HealthNational Institutes of Health National Institute of Allergy and Infectious DiseasesAmerican Surgical Association FoundationBurroughs Wellcome FundNational Institute of Dental and Craniofacial ResearchDigestive Diseases Reseach Core Center, University of ChicagoCalifornia Institute for Regenerative MedicineNIAMS NIH HHSNIH HHSDigestive Diseases Research Core Center, University of ChicagoNational Institute of Arthritis and Musculoskeletal and Skin DiseasesNew York Stem Cell FoundationPEW Charitable TrustsNational Institute of Diabetes and Digestive and Kidney DiseasesAmerican College of SurgeonsNIAID NIH HHSNIDDK NIH HHSScleroderma Research FoundationNIGMS NIH HHSStanford Maternal and Child Health Research InstituteReed Foundation6536-6553.e26https://www.ebi.ac.uk/biostudies/studies/S-EPMC12453597biostudies-literatureUnknown188(23)A significant complication of Crohn's disease (CD) is intestinal fibrosis, which narrows the bowel lumen to form a stricture. Creeping fat (CF) is the wrapping of mesenteric adipose tissue around diseased bowel, of which the role in CD stricture progression is unclear. By constructing a human single-cell CD fibroblast atlas, we identified CF-derived, CTHRC1+ fibroblasts enriched for Yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ) signatures and localized to a fibrotic CF-bowel wall interface within the stricture. We further showed that analogous Cthrc1+ mouse fibroblasts derive from mesenteric adipose tissue stromal cells, infiltrate fibrotic bowel, and deposit extracellular matrix in a YAP/TAZ-dependent manner in a mouse model of intestinal fibrosis.CellCreeping fat-derived mechanosensitive fibroblasts drive intestinal fibrosis in Crohn's disease strictures.PMC12453597R01 AR081343R01 DE032677R01 GM136659R01 AI184905U24 DE029463P30 DK097948RO1 DK 125293R01-DE032677R01-AR081343S10-OD016164T32 GM145402R01-GM136659R01AI184905R01 DE021683R01 DK125293S10 OD016164R01 AI16846200034119R01AI168462U24DE029463Sidhu INaik SLLongaker MTHyun JSKim AFoster DSPizarro TTWan DCXing YGoyal AGuo JLBauer-Rowe KEPham BLiang NEPrystupa AKorah MJanuszyk MNorton JAGriffin MSuh EJLu JMDe Santis SDelitto DfalseCreeping fat-derived mechanosensitive fibroblasts drive intestinal fibrosis in Crohn's disease strictures.A significant complication of Crohn's disease (CD) is intestinal fibrosis, which narrows the bowel lumen to form a stricture. Creeping fat (CF) is the wrapping of mesenteric adipose tissue around diseased bowel, of which the role in CD stricture progression is unclear. By constructing a human single-cell CD fibroblast atlas, we identified CF-derived, CTHRC1+ fibroblasts enriched for Yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ) signatures and localized to a fibrotic CF-bowel wall interface within the stricture. We further showed that analogous Cthrc1+ mouse fibroblasts derive from mesenteric adipose tissue stromal cells, infiltrate fibrotic bowel, and deposit extracellular matrix in a YAP/TAZ-dependent manner in a mouse model of intestinal fibrosis.2025-01-01T00:00:00Z2025 Nov2026-06-13T05:08:22.283Z2026-06-13T03:09:04.627ZS-EPMC124535974096721510.1016/j.cell.2025.08.029