Single cell sequencing data on ileum and mesentery tissue from Crohn's disease patients
Download from source ↗Dataset overview
Distinct roles for B cell-derived LTα3 and LTα1β2 in TNF-mediated ileitis.
Abstract
Crohn's disease pathology is modeled in TNF<sup>ΔARE+/-</sup> mice that overproduce tumor necrosis factor (TNF) to drive disease through TNF receptors. An alternative ligand for TNF receptors, soluble LTα<sub>3</sub>, is produced by B cells, but has received scarce attention because LTα also partners with LTβ to generate membrane-tethered LTαβ<sub>2</sub> that promotes tertiary lymphoid tissue-another feature of Crohn's disease. We hypothesized that B cell-derived LTαβ<sub>2</sub> would critically affect ileitis in TNF<sup>ΔARE+/-</sup> mice. However, whereas deleting LTβ in B cells was essential for tertiary lymphoid tissue, disease pathology was minimally affected. By contrast, loss of B cell-derived LTα increased intestinal permeability, shrunk the pool of IgA<sup>+</sup> ileal plasma cells, elevated cytokines and prompted weight loss, including loss of muscle mass-a systemic feature of Crohn's disease. Neutralizing antibodies to LTα<sub>3</sub> strongly augmented the cachexic-like effects of TNF. Thus, B cell-produced LTαβ<sub>2</sub> and LTα<sub>3</sub> have distinct roles in ileitis, with the role of LTα<sub>3</sub> unexpectedly protective through counterbalancing TNF.
doi:10.1038/s41590-025-02263-y ↗ PMID 40921841 ↗ PMC12479355 ↗
Study facts
- Organism
- Homo sapiens
- Platform
- 10x Genomics Chromium
- Age group
- —
- Disease groups
- —
- Anatomical sites
- ileum, mesentery
Data availability
- Raw counts
- Processed matrix
- Analysis code
File types
CSVMTXTSV
Files and samples
- filelist.txt ↗
- GSE255722_RAW.tar ↗
- GSM8078396_CTL001_NI_ILEUM_RNA_barcodes.tsv.gz ↗
- GSM8078396_CTL001_NI_ILEUM_RNA_features.tsv.gz ↗
- GSM8078396_CTL001_NI_ILEUM_RNA_matrix.mtx.gz ↗
- GSM8078397_CTL001_NI_ILEUM_BCR_filtered_contig_annotations.csv.gz ↗
- GSM8078398_CTL001_NI_ILEUM_TCR_filtered_contig_annotations.csv.gz ↗
- GSM8078399_CTL001_NI_MES_RNA_barcodes.tsv.gz ↗
- GSM8078399_CTL001_NI_MES_RNA_features.tsv.gz ↗
- GSM8078399_CTL001_NI_MES_RNA_matrix.mtx.gz ↗
- GSM8078400_CTL001_NI_MES_TCR_filtered_contig_annotations.csv.gz ↗
- GSM8078401_CTL002_NI_MES_RNA_barcodes.tsv.gz ↗
- GSM8078401_CTL002_NI_MES_RNA_features.tsv.gz ↗
- GSM8078401_CTL002_NI_MES_RNA_matrix.mtx.gz ↗
- GSM8078402_CTL002_NI_MES_BCR_filtered_contig_annotations.csv.gz ↗
- GSM8078403_CTL002_NI_MES_TCR_filtered_contig_annotations.csv.gz ↗
- GSM8078404_CD003_INF_MES_RNA_barcodes.tsv.gz ↗
- GSM8078404_CD003_INF_MES_RNA_features.tsv.gz ↗
- GSM8078404_CD003_INF_MES_RNA_matrix.mtx.gz ↗
- GSM8078405_CD003_INF_MES_BCR_filtered_contig_annotations.csv.gz ↗
- GSM8078406_CD003_INF_MES_TCR_filtered_contig_annotations.csv.gz ↗
- GSM8078407_CD003_NI_MES_RNA_barcodes.tsv.gz ↗
- GSM8078407_CD003_NI_MES_RNA_features.tsv.gz ↗
- GSM8078407_CD003_NI_MES_RNA_matrix.mtx.gz ↗
- GSM8078408_CD003_NI_MES_BCR_filtered_contig_annotations.csv.gz ↗
- GSM8078409_CD003_NI_MES_TCR_filtered_contig_annotations.csv.gz ↗
- GSM8078410_CD004_INF_ILEUM_RNA_barcodes.tsv.gz ↗
- GSM8078410_CD004_INF_ILEUM_RNA_features.tsv.gz ↗
- GSM8078410_CD004_INF_ILEUM_RNA_matrix.mtx.gz ↗
- GSM8078411_CD004_INF_ILEUM_BCR_filtered_contig_annotations.csv.gz ↗
- GSM8078412_CD004_INF_ILEUM_TCR_filtered_contig_annotations.csv.gz ↗
- GSM8078413_CD004_NI_ILEUM_RNA_barcodes.tsv.gz ↗
- GSM8078413_CD004_NI_ILEUM_RNA_features.tsv.gz ↗
- GSM8078413_CD004_NI_ILEUM_RNA_matrix.mtx.gz ↗
- GSM8078414_CD004_NI_ILEUM_BCR_filtered_contig_annotations.csv.gz ↗
- GSM8078415_CD004_NI_ILEUM_TCR_filtered_contig_annotations.csv.gz ↗
- GSM8078416_CD004_INF_MES_RNA_barcodes.tsv.gz ↗
- GSM8078416_CD004_INF_MES_RNA_features.tsv.gz ↗
- GSM8078416_CD004_INF_MES_RNA_matrix.mtx.gz ↗
- GSM8078417_CD004_INF_MES_BCR_filtered_contig_annotations.csv.gz ↗
- GSM8078418_CD004_INF_MES_TCR_filtered_contig_annotations.csv.gz ↗
- GSM8078419_CD004_NI_MES_RNA_barcodes.tsv.gz ↗
- GSM8078419_CD004_NI_MES_RNA_features.tsv.gz ↗
- GSM8078419_CD004_NI_MES_RNA_matrix.mtx.gz ↗
- GSM8078420_CD004_NI_MES_BCR_filtered_contig_annotations.csv.gz ↗
- GSM8078421_CD005_INF_ILEUM_RNA_barcodes.tsv.gz ↗
- GSM8078421_CD005_INF_ILEUM_RNA_features.tsv.gz ↗
- GSM8078421_CD005_INF_ILEUM_RNA_matrix.mtx.gz ↗
- GSM8078422_CD005_INF_ILEUM_BCR_filtered_contig_annotations.csv.gz ↗
- GSM8078423_CD005_INF_ILEUM_TCR_filtered_contig_annotations.csv.gz ↗
- GSM8078424_CD005_NI_ILEUM_RNA_barcodes.tsv.gz ↗
- GSM8078424_CD005_NI_ILEUM_RNA_features.tsv.gz ↗
- GSM8078424_CD005_NI_ILEUM_RNA_matrix.mtx.gz ↗
- GSM8078425_CD005_NI_ILEUM_BCR_filtered_contig_annotations.csv.gz ↗
- GSM8078426_CD005_NI_ILEUM_TCR_filtered_contig_annotations.csv.gz ↗
- GSM8078427_CD005_INF_MES_RNA_barcodes.tsv.gz ↗
- GSM8078427_CD005_INF_MES_RNA_features.tsv.gz ↗
- GSM8078427_CD005_INF_MES_RNA_matrix.mtx.gz ↗
- GSM8078428_CD005_INF_MES_BCR_filtered_contig_annotations.csv.gz ↗
- GSM8078429_CD005_INF_MES_TCR_filtered_contig_annotations.csv.gz ↗
- GSM8078430_CD005_NI_MES_RNA_barcodes.tsv.gz ↗
- GSM8078430_CD005_NI_MES_RNA_features.tsv.gz ↗
- GSM8078430_CD005_NI_MES_RNA_matrix.mtx.gz ↗
- GSM8078431_CD005_NI_MES_BCR_filtered_contig_annotations.csv.gz ↗
- GSM8078432_CD005_NI_MES_TCR_filtered_contig_annotations.csv.gz ↗
- index.html ↗
- Mesentery22
- Ileum15
| Accession | Sample | Tissue | Molecule |
|---|---|---|---|
GSM8078396 |
Ileum, Control, Non-inflamed, rep 1, scRNA-seq | Ileum | total RNA |
GSM8078397 |
Ileum, Control, Non-inflamed, rep 1, scBCR-seq | Ileum | total RNA |
GSM8078398 |
Ileum, Control, Non-inflamed, rep 1, scTCR-seq | Ileum | total RNA |
GSM8078399 |
Mesentery, Control, Non-inflamed, rep 1, scRNA-seq | Mesentery | total RNA |
GSM8078400 |
Mesentery, Control, Non-inflamed, rep 1, scTCR-seq | Mesentery | total RNA |
GSM8078401 |
Mesentery, Control, Non-inflamed, rep 2, scRNA-seq | Mesentery | total RNA |
GSM8078402 |
Mesentery, Control, Non-inflamed, rep 2, scBCR-seq | Mesentery | total RNA |
GSM8078403 |
Mesentery, Control, Non-inflamed, rep 2, scTCR-seq | Mesentery | total RNA |
GSM8078404 |
Mesentery, Crohn's disease, Inflamed, rep 1, scRNA-seq | Mesentery | total RNA |
GSM8078405 |
Mesentery, Crohn's disease, Inflamed, rep 1, scBCR-seq | Mesentery | total RNA |
GSM8078406 |
Mesentery, Crohn's disease, Inflamed, rep 1, scTCR-seq | Mesentery | total RNA |
GSM8078407 |
Mesentery, Crohn's disease, Non-inflamed, rep 1, scRNA-seq | Mesentery | total RNA |
GSM8078408 |
Mesentery, Crohn's disease, Non-inflamed, rep 1, scBCR-seq | Mesentery | total RNA |
GSM8078409 |
Mesentery, Crohn's disease, Non-inflamed, rep 1, scTCR-seq | Mesentery | total RNA |
GSM8078410 |
Ileum, Crohn's disease, Inflamed, rep 2, scRNA-seq | Ileum | total RNA |
GSM8078411 |
Ileum, Crohn's disease, Inflamed, rep 2, scBCR-seq | Ileum | total RNA |
GSM8078412 |
Ileum, Crohn's disease, Inflamed, rep 2, scTCR-seq | Ileum | total RNA |
GSM8078413 |
Ileum, Crohn's disease, Non-inflamed, rep 2, scRNA-seq | Ileum | total RNA |
GSM8078414 |
Ileum, Crohn's disease, Non-inflamed, rep 2, scBCR-seq | Ileum | total RNA |
GSM8078415 |
Ileum, Crohn's disease, Non-inflamed, rep 2, scTCR-seq | Ileum | total RNA |
GSM8078416 |
Mesentery, Crohn's disease, Inflamed, rep 2, scRNA-seq | Mesentery | total RNA |
GSM8078417 |
Mesentery, Crohn's disease, Inflamed, rep 2, scBCR-seq | Mesentery | total RNA |
GSM8078418 |
Mesentery, Crohn's disease, Inflamed, rep 2, scTCR-seq | Mesentery | total RNA |
GSM8078419 |
Mesentery, Crohn's disease, Non-inflamed, rep 2, scRNA-seq | Mesentery | total RNA |
GSM8078420 |
Mesentery, Crohn's disease, Non-inflamed, rep 2, scBCR-seq | Mesentery | total RNA |
GSM8078421 |
Ileum, Crohn's disease, Inflamed, rep 3, scRNA-seq | Ileum | total RNA |
GSM8078422 |
Ileum, Crohn's disease, Inflamed, rep 3, scBCR-seq | Ileum | total RNA |
GSM8078423 |
Ileum, Crohn's disease, Inflamed, rep 3, scTCR-seq | Ileum | total RNA |
GSM8078424 |
Ileum, Crohn's disease, Non-inflamed, rep 3, scRNA-seq | Ileum | total RNA |
GSM8078425 |
Ileum, Crohn's disease, Non-inflamed, rep 3, scBCR-seq | Ileum | total RNA |
GSM8078426 |
Ileum, Crohn's disease, Non-inflamed, rep 3, scTCR-seq | Ileum | total RNA |
GSM8078427 |
Mesentery, Crohn's disease, Inflamed, rep 3, scRNA-seq | Mesentery | total RNA |
GSM8078428 |
Mesentery, Crohn's disease, Inflamed, rep 3, scBCR-seq | Mesentery | total RNA |
GSM8078429 |
Mesentery, Crohn's disease, Inflamed, rep 3, scTCR-seq | Mesentery | total RNA |
GSM8078430 |
Mesentery, Crohn's disease, Non-inflamed, rep 3, scRNA-seq | Mesentery | total RNA |
GSM8078431 |
Mesentery, Crohn's disease, Non-inflamed, rep 3, scBCR-seq | Mesentery | total RNA |
GSM8078432 |
Mesentery, Crohn's disease, Non-inflamed, rep 3, scTCR-seq | Mesentery | total RNA |
Strengths & limitations for reuse
Strengths
- Raw reads are advertised
- Raw counts are advertised
- Processed matrices are advertised
- Analysis code is available
- Participant mapping is available
- Participant counts are documented
Limitations
- Not documented: cell metadata are advertised
Extraction evidence & provenance
Each extracted field is shown with the source excerpt and location used to resolve it.
Assay
| Field | Value | Evidence |
|---|---|---|
assay.assay_type |
5' RNA expression |
For sample preparation on the 10x Genomics platform, the Chromium Next GEM Single Cell 5′ Kit v.2 was used for mouse cells and Chromium Single Cell 5′ Library Kit was used for human cells Section |
assay.library_chemistry |
Chromium Single Cell 5' Library Kit |
Chromium Single Cell 5' Library Kit was used for human cells Section |
assay.platform |
10x Genomics Chromium |
For sample preparation on the 10x Genomics platform Section |
assay.reference_genome |
GRCh38-2020-A |
Assembly: GRCh38-2020-A for 5' RNA expression Section |
assay.sequencing_type |
scrna_seq |
Single cell RNA sequencing (scRNA-seq) of sorted live, CD45 + mesenteric cells Section |
Cohort
| Field | Value | Evidence |
|---|---|---|
cohort.crohns_disease_participants |
3 |
Single cell RNA sequencing (scRNA-seq) of sorted live, CD45 + mesenteric cells from 3 CD patients with matched mesentery draining from inflamed and non-inflamed regions of the ileum. Section |
cohort.disease_activity_metadata_available |
True |
paired inflamed ileal-draining mesentery surgical samples and non-inflamed ileal-draining mesentery surgical samples Section |
cohort.non_ibd_controls |
2 inferred |
Control (Gastrointestinal cancer) Section |
cohort.study_design |
cross_sectional inferred |
We used single cell RNA sequencing to compare the immune cells in paired inflamed ileal-draining mesentery surgical samples and non-inflamed ileal-draining mesentery surgical samples Section |
cohort.total_participants |
5 inferred |
Ileum and the associated mesentery was also collected from gastrointestinal cancer patients Section |
Data_Assets
| Field | Value | Evidence |
|---|---|---|
data_assets.analysis_code |
True |
Customized code for both analysis of the scRNA-seq data and generation of some of the figures is available via GitHub Section |
data_assets.open_access |
True |
De-identified human scRNA-seq data analyzed in this study are publicly available in the Gene Expression Omnibus (GEO) database ( GSE255722 ). Section |
data_assets.participant_metadata |
True |
Excel sheet showing the age, sex and tissue type obtained from patients for human experiments. Section |
data_assets.processed_matrix |
True |
RNA_matrix.mtx.gz Section |
data_assets.raw_counts |
True |
Supplementary files format and content: Tab-seperated values files and matrix files for the 5' RNA data Section |
data_assets.raw_reads |
True |
GSE255722_RAW.tar Section |
Processing
| Field | Value | Evidence |
|---|---|---|
processing.cell_type_annotation_method |
cell identity assigned based on expression features |
Cells expressing LTA included naive B cells, memory B cells, plasma cells, several subpopulations of memory T cells and some plasmacytoid dendritic cells. Section |
processing.doublet_detection_reported |
True inferred |
scDblFinder 64 (v.1.2.0) Section |
processing.quality_control_reported |
True |
Dead cells were excluded using a Live/Dead Aqua Fixable Cell Stain Kit Section |
Specimens
| Field | Value | Evidence |
|---|---|---|
specimens.anatomical_sites |
['ileum', 'mesentery'] |
Ileum and the attached mesentery was collected Section |
specimens.inflamed_status_available |
True |
paired inflamed ileal-draining mesentery surgical samples and non-inflamed ileal-draining mesentery surgical samples Section |
specimens.number_of_samples |
13 |
"library_strategy": {"OTHER": 24, "RNA-Seq": 13} Section |
specimens.participant_to_sample_mapping_available |
True |
from 3 CD patients with matched mesentery draining from inflamed and non-inflamed regions of the ileum Section |
specimens.specimen_type |
resection |
Discarded human mesentery tissues came from patients with CD that were undergoing bowel resections at Washington University School of Medicine. Section |