Creeping fat-derived mechanosensitive fibroblasts drive intestinal fibrosis in Crohn’s disease strictures [Visium]
A significant complication of Crohn’s disease (CD) is intestinal fibrosis, which narrows the bowel lumen to cause a stricture. Creeping fat (CF) is the wrapping of mesenteric adipose tissue (MAT) around inflamed and fibrotic bowel, but its role in stricture progression in CD is unclear. In this study, we explore whether CF-derived fibroblasts, the cells primarily responsible for extracellular matrix (ECM) deposition, directly contribute to stricture progression. By performing scRNA-seq and Visium on pediatric CD strictures, we identified a CF-associated, mechanosensitive, CTHRC1+ fibroblast enriched for YAP/TAZ signaling that localized to the fibrotic CF-bowel wall interface within the stricture. We developed a novel mouse model of intestinal fibrosis that exhibited CF and used lineage tracing to show that Postn+ mouse fibroblasts, analogous to human CTHRC1+ fibroblasts, infiltrate fibrotic bowel and deposit ECM in a YAP/TAZ-dependent manner through scRNA-seq. Our findings identify mesenteric fat as a key source of pro-fibrotic fibroblasts that can be therapeutically targeted to limit intestinal fibrosis.
from sddb import Catalog
cohort = Catalog().collection("geo-gse275144")
cohort.members # the 2 datasets as a table
print(cohort.licenses()) # check the terms before you download
sdatas = cohort.to_dict() # {uid: SpatialData}, cached locally
# or keep the .zarr files in a folder of your choice:
# sdatas = cohort.to_dict(dest="data/") Needs pip install lamindb and network access to the Lamin database, which is limited during the alpha. If it fails, use the Client tab.
import lamindb as ln
db = ln.DB("scverse/spatialdata-db")
coll = db.Collection.get(key="geo-gse275144")
coll.ordered_artifacts.to_dataframe() # the 2 members, ordered
# download every member .zarr to the local cache:
paths = [a.cache() for a in coll.ordered_artifacts.all()] # sddb client: download every member .zarr into data/
sddb-cli download --collection geo-gse275144 --dest data/ Licenses: 2 NCBI GEO policy
Cite this collection
doi.org/10.1016/j.cell.2025.08.029 ↗@article{Bauer_Rowe_2025,
title = {Creeping fat-derived mechanosensitive fibroblasts drive intestinal fibrosis in Crohn’s disease strictures},
volume = {188},
ISSN = {0092-8674},
url = {http://dx.doi.org/10.1016/j.cell.2025.08.029},
DOI = {10.1016/j.cell.2025.08.029},
number = {23},
journal = {Cell},
publisher = {Elsevier BV},
author = {Bauer-Rowe, Khristian E. and Pham, Benjamin and Griffin, Michelle and Liang, Norah E. and Kim, Alexia and Lu, John M. and Januszyk, Michael and Guo, Jason L. and De Santis, Stefania and Xing, Yue and Prystupa, Aleksandr and Sidhu, Ikjot and Suh, Elijah J. and Foster, Deshka S. and Korah, Maria and Goyal, Alka and Wan, Derrick C. and Norton, Jeffrey A. and Delitto, Daniel and Pizarro, Theresa T. and Naik, Shruti L. and Hyun, Jeong S. and Longaker, Michael T.},
year = {2025},
month = Nov,
pages = {6536–6553.e26}
}