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A longitudinal single-cell atlas of anti-tumour necrosis factor treatment in inflammatory bowel disease

GSE282122 Homo sapiens Expression profiling by high throughput sequencing 216 samples Submitted 2024/11/19 Platform GPL24676
Summary
Precision medicine in immune-mediated inflammatory diseases (IMIDs) requires a cellular understanding of treatment response. We describe a therapeutic atlas for Crohn’s disease (CD) and ulcerative colitis (UC) following adalimumab, an anti-tumour necrosis factor (anti-TNF) treatment. We generated ~1 million single-cell transcriptomes, organised into 109 cell states, from 216 gut biopsies (41 subjects), revealing disease-specific differences. A systems biology-spatial analysis identified granuloma signatures in CD and interferon (IFN)-response signatures localising to T cell aggregates and epithelial damage in CD and UC. Pretreatment differences in epithelial and myeloid compartments were associated with remission outcomes in both diseases. Longitudinal comparisons demonstrated disease progression in nonremission: myeloid and T cell perturbations in CD and increased multi-cellular IFN signalling in UC. IFN signalling was also observed in rheumatoid arthritis (RA) synovium with a lymphoid pathotype. Our therapeutic atlas represents the largest cellular census of perturbation with the most common biologic treatment, anti-TNF, across multiple inflammatory diseases.
Published in
A longitudinal single-cell atlas of anti-tumour necrosis factor treatment in inflammatory bowel disease
Thomas T, Friedrich M, Rich-Griffin C et al. · Nature immunology 2024 · PMID 39438660 · doi:10.1038/s41590-024-01994-8
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Direct links to NCBI, no account and no request form: the whole study as GSE282122_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 216 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1179412 and SRA study SRP541799. Searching any of these in the dataset finder brings you back here.

Study design
40 conditions, each sampled once — no replicated groups

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