Creeping fat-derived mechanosensitive fibroblasts drive intestinal fibrosis in Crohn’s disease strictures [Xenium]
Download from source ↗Dataset overview
Creeping fat-derived mechanosensitive fibroblasts drive intestinal fibrosis in Crohn's disease strictures.
Abstract
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. Our findings identify CF as a key source of pro-fibrotic fibroblasts and raise the possibility of improving future clinical management of stricture progression by targeting not only the bowel but also CF.
doi:10.1016/j.cell.2025.08.029 ↗ PMID 40967215 ↗ PMC12453597 ↗
Study facts
- Organism
- Homo sapiens
- Platform
- 10x Genomics Xenium
- Age group
- paediatric
- Disease groups
- —
- Anatomical sites
- Intestinal Stricture, Normal Bowel
Data availability
- Processed matrix
- Histology images
File types
H5PARQUETTIFF
Files and samples
- Small Intestine8
| Accession | Sample | Tissue | Molecule |
|---|---|---|---|
GSM8968701 |
Region_1_0038414_Stricture | Small Intestine | other |
GSM8968702 |
Region_2_0038414_Uninvolved | Small Intestine | other |
GSM8968703 |
Region_1_0038438_Stricture | Small Intestine | other |
GSM8968704 |
Region_2_0038438_Uninvolved | Small Intestine | other |
GSM8968705 |
Region_1_0038555_Stricture | Small Intestine | other |
GSM8968706 |
Region_2_0038555_Stricture | Small Intestine | other |
GSM8968707 |
Region_1_0038556_Stricture | Small Intestine | other |
GSM8968708 |
Region_2_0038556_Uninvolved | Small Intestine | other |
Strengths & limitations for reuse
Strengths
- Processed matrices are advertised
- Histology images are advertised
Limitations
- Not documented: raw counts are advertised
- Not documented: spatial coordinates are advertised
- Not documented: participant counts are documented
Extraction evidence & provenance
Each extracted field is shown with the source excerpt and location used to resolve it.
Assay
| Field | Value | Evidence |
|---|---|---|
assay.panel_size |
470 |
with 470 custom gene probes Section |
assay.platform |
10x Genomics Xenium |
Spatial transcriptomics of human bowel and mesenteric adipose tissue using the 10X Genomics Xenium platform Section |
assay.resolution |
cellular |
imaging to identify the RNA within each cell of a tissue Section |
assay.segmentation_method |
Cell segmentation after staining |
Custom gene probes were added to tissue samples to hybridize with target RNA and then stained to perform cell segmentation. Section |
assay.sequencing_based |
False inferred |
Samples are then run on a Xenium Analyzer with performs fluorescent probe hybridization and imaging Section |
assay.whole_transcriptome |
False |
using the 10X Genomics Xenium platform with 470 custom gene probes Section |
Cohort
| Field | Value | Evidence |
|---|---|---|
cohort.age_group |
paediatric |
By performing scRNA-seq, Visium and Xenium on pediatric CD strictures Section |
Data_Assets
| Field | Value | Evidence |
|---|---|---|
data_assets.file_manifest |
True |
filelist.txt Section |
data_assets.histology_images |
True from source |
GEO deposit evidence: TIFF in GEO suppfile types Section |
data_assets.open_access |
True |
Public on Sep 17 2025 Section |
data_assets.processed_matrix |
True from source |
GEO deposit evidence: H5 in GEO suppfile types Section |
Specimens
| Field | Value | Evidence |
|---|---|---|
specimens.anatomical_sites |
['Intestinal Stricture', 'Normal Bowel'] from source |
GEO sample source names: Intestinal Stricture; Normal Bowel Section |
specimens.inflamed_status_available |
True |
Region_1_0038414_Stricture ... source_name: Intestinal Stricture; Region_2_0038414_Uninvolved ... source_name: Normal Bowel Section |
specimens.number_of_samples |
8 computed |
8 GSM records parsed from GEO family SOFT Section |
specimens.preservation_method |
Flash-frozen in OCT; cryosectioned at -20°C |
we flash froze tissue samples in OCT ... Tissues were cyrosectioned at -20C onto Xenium slide Section |