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Accute and repeated DSS exposure induce distinct immune responses with differential relevance to human Ulcerative Colitis

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Dataset overview

Participants 6
Samples 10
Reuse readiness 7.6/10 evidence-backed score

Repeated Dextran Sulfate Sodium Exposure Elicits Distinct Immune Responses Reflecting Human Ulcerative Colitis.

Manzanares LD, Dehghani Z, Herrnreiter CJ, Ren X, Sumagin ME, Serdiukova A, Naqib A, Green S, et al. · Cellular and molecular gastroenterology and hepatology · 2025

Abstract

<h4>Background & aims</h4>Dextran sulfate sodium (DSS)-induced colitis is a widely used model to study ulcerative colitis (UC). However, the extent to which acute vs repeated DSS exposure mimics human disease remains unclear.<h4>Methods</h4>Using histopathology, flow cytometry, single-cell RNA sequencing (scRNA-seq), and 16S rRNA profiling, we compared disease outcomes, immune infiltrate, transcriptional programs, and changes in the microbiome in mice subjected to a single (acute) vs 2 (repeated) DSS cycles. We further evaluated which experimental condition better represents key immune cell subtype states in human disease.<h4>Results</h4>Although disease activity indices were similar between groups, repeated DSS exposure resulted in greater colon shortening, mucosal remodeling, and elevated immune infiltration, particularly by neutrophils (PMNs) in the distal colon. scRNA-seq revealed that PMNs and T cells acquired distinct transcriptional programs in repeated vs acute colitis. Cycle 1 PMNs showed inflammatory and cytotoxic signatures, whereas cycle 2 PMNs were enriched in tissue remodeling and survival pathways. CD4 and CD8 T cells in repeated colitis exhibited migratory, and pathogen-responsive phenotypes, with expanded regulatory T cells and exhausted CD8 subsets. In contrast, macrophage numbers decreased with repeated DSS, though remaining cells exhibited pro-resolution gene expression profiles. Microbiome analysis revealed normalization trends with repeated DSS exposure, including reduced proinflammatory and increased beneficial genera. Cross-species transcriptomic comparisons indicated cycle-specific overlap with human UC, where cycle 2 activated PMNs and alternatively activated macrophages, closer aligned with active human UC.<h4>Conclusions</h4>Collectively, our data indicate that repeated DSS cycles provide a better experimental colitis model for studying immune cells in UC and identifying distinct immune subtypes relevant to UC therapeutics.

doi:10.1016/j.jcmgh.2025.101714 ↗ PMID 41453640 ↗ PMC12892045 ↗

Study facts

Organism
Homo sapiens; Mus musculus
Platform
Illumina NovaSeq X Plus
Age group
—
Disease groups
—
Anatomical sites
colon

Data availability

  • Raw counts
  • Processed matrix

File types MTXTSV

Strengths & limitations for reuse

Strengths

  • Raw reads are advertised
  • Raw counts are advertised
  • Processed matrices are advertised
  • Cell metadata are advertised
  • Participant counts are documented
Extraction evidence & provenance

Each extracted field is shown with the source excerpt and location used to resolve it.

Assay

FieldValueEvidence
assay.assay_type RNA-Seq
Expression profiling by high throughput sequencing

Section series metadata, offset —
assay.library_chemistry 10x Genomics Single Cell 3′ Reagents kit v3
Libraries for both human and mouse samples were generated using Genomics Single Cell 3′ Reagents kit (v3)

Section sample_values_with_sample_counts, offset —
assay.platform Illumina NovaSeq X Plus
Illumina NovaSeq X Plus

Section —, offset —
assay.reference_genome GRCh38; GRCm38
aligned to either Mus musculus reference genome (GRCm38) or human GRCh38

Section Single-cell data processing, offset —
assay.sequencing_type scrna_seq
we performed a single-cell mRNA sequencing (scRNA-seq)

Section Results, offset —

Cohort

FieldValueEvidence
cohort.disease_activity_metadata_available True
Human colonic biopsies were obtained from consented inactive UC patients (Mayo endoscopic scores of 0)

Section samples, offset —
cohort.total_participants 6
integrating 4 patients with active disease and 6 patients in remission

Section Cross-species Gene Module Assessment, offset —
cohort.treatment_exposure_documented True from source
GEO sample characteristics document treatment/therapy

Section GEO family SOFT, offset —
cohort.ulcerative_colitis_participants 6
"Inactive UC": 6

Section sample_values_with_sample_counts, offset —

Data_Assets

FieldValueEvidence
data_assets.cell_metadata True
tab-delimited text file includes cell and gene unique identifiers

Section samples, offset —
data_assets.open_access True
Public on Oct 31 2025

Section —, offset —
data_assets.processed_matrix True
Supplementary files format and content: mtx file contains counts for each sample

Section samples, offset —
data_assets.raw_counts True
Supplementary files format and content: mtx file contains counts for each sample

Section —, offset —
data_assets.raw_reads True
GSE306845_RAW.tar

Section —, offset —

Processing

FieldValueEvidence
processing.batch_correction_reported True
integration using harmony

Section Materials and Methods; Single-cell data analysis, offset —
processing.cell_type_annotation_method differentially expressed genes and common lineage markers
annotated into cell types based on differentially expressed genes (DEGs) and common lineage markers

Section Repeated DSS Exposure Triggers Acquisition of Differential Transcriptional Programs in Colon-infiltrating PMNs, offset —
processing.normalization_method sctransform
Data was normalized and scaled using sctransform

Section Materials and Methods; Single-cell data analysis, offset —
processing.quality_control_reported True
Each sample was filtered using a dynamic per-sample upper limit for gene count, UMI count, and percent ribosomal genes

Section Materials and Methods; Single-cell data processing, offset —

Specimens

FieldValueEvidence
specimens.anatomical_sites ['colon']
RNA seq profiling of colonic biopsies of inactive UC patients and colon digest of C57/BL/6J mice

Section —, offset —
specimens.inflamed_status_available True
"treatment": "Inactive UC"

Section samples, offset —
specimens.number_of_cells 79238 inferred
After filtering, 51,464 (55%) of human and 27,774 (78%) of mouse cells remained

Section Single-cell data processing, offset —
specimens.number_of_samples 10
"sample_count": 10

Section dataset authority, offset —
specimens.specimen_type mixed
RNA seq profiling of colonic biopsies of inactive UC patients and colon digest of C57/BL/6J mice during 1 cycle and 2 cycles (2.5%) DSS.

Section series_overall_design, offset —