Single cell sequencing data on ileum and mesentery tissue from Crohn's disease patients

Dataset overview

Participants None

Samples 37

Reuse readiness 5.6/10 evidence-backed score

Distinct roles for B cell-derived LTα3 and LTα1β2 in TNF-mediated ileitis.

Erlich EC, Alayo QA, Kim A, Han J, Mintz RL, Huckstep CG, Ruiz HS, Field RL, et al. · Nature immunology · 2025

Abstract

Crohn's disease pathology is modeled in TNFΔARE+/- mice that overproduce tumor necrosis factor (TNF) to drive disease through TNF receptors. An alternative ligand for TNF receptors, soluble LTα3, is produced by B cells, but has received scarce attention because LTα also partners with LTβ to generate membrane-tethered LTαβ2 that promotes tertiary lymphoid tissue-another feature of Crohn's disease. We hypothesized that B cell-derived LTαβ2 would critically affect ileitis in TNFΔARE+/- 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+ ileal plasma cells, elevated cytokines and prompted weight loss, including loss of muscle mass-a systemic feature of Crohn's disease. Neutralizing antibodies to LTα3 strongly augmented the cachexic-like effects of TNF. Thus, B cell-produced LTαβ2 and LTα3 have distinct roles in ileitis, with the role of LTα3 unexpectedly protective through counterbalancing TNF.

doi:10.1038/s41590-025-02263-y ↗ PMID 40921841 ↗ PMC12479355 ↗

Study facts

Organism: Homo sapiens
Platform: single-cell RNA sequencing
Age group: —
Disease groups: —
Anatomical sites: ileum, mesentery

Data availability

Processed matrix
Analysis code

File types CSVMTXTSV

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
Processed matrices are advertised
Analysis code is available
Participant mapping is available

Limitations

Not documented: raw counts are advertised
Not documented: cell metadata 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.assay_type`	single-cell RNA sequencing	Single-cell RNA profiling Section `Methods—Single-cell RNA profiling`, offset —
`assay.library_chemistry`	10x Genomics Chromium Single Cell 5' Library and Gel Bead Kit	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 `Methods—Single-cell RNA profiling`, offset —
`assay.reference_genome`	GRCh38-2020-A	For the human data, raw sequencing data were processed using the Cell Ranger multipipeline, v.7.1.0 (10x Genomics) using the human reference genome GRCh38-2020-A. Section `Methods—Single-cell RNA profiling`, offset —
`assay.sequencing_type`	scrna_seq	Mesentery, Crohn's disease, Inflamed, rep 1, scRNA-seq Section `—`, offset —

Cohort

Field Value Evidence

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 `Results`, offset —

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 Results, offset —

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 Availability Statement`, offset —
`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 availability`, offset —
`data_assets.participant_metadata`	True	Excel sheet showing the age, sex and tissue type obtained from patients for human experiments. Section `Associated Data`, offset —
`data_assets.processed_matrix`	True	RNA_matrix.mtx.gz Section `—`, offset —
`data_assets.raw_reads`	True	GSE255722_RAW.tar Section `geo_document`, offset —

Specimens

Field	Value	Evidence
`specimens.anatomical_sites`	['ileum', 'mesentery']	Single cell sequencing data on ileum and mesentery tissue from Crohn's disease patients Section `geo_record_summary`, offset —
`specimens.number_of_samples`	37	"n_samples": 37 Section `geo_record_summary`, offset —
`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 `Results`, offset —
`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 `Methods—Patient samples`, offset —