Unveiling the Cellular and Molecular Insights into Ulcerative Colitis Pathogenesis through Integrative Multi-omics
Yi Han1,2, Junbo Xiao1,2, Jun Yi1,2
1Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
Combinatorial Chemistry & High Throughput Screening
|July 3, 2026
Summary
This study identifies ING4 as a potential causal gene in ulcerative colitis (UC) pathogenesis. Integrating multi-omics data reveals ING4
Area of Science:
- Genomics and Molecular Biology
- Immunology and Inflammation
- Gastroenterology
Background:
- Single-cell RNA sequencing (scRNA-seq) reveals cellular heterogeneity in ulcerative colitis (UC).
- Causal relationships between differentially expressed genes (DEGs) and UC pathogenesis require further elucidation.
- Comprehensive multi-omics integration is needed to understand UC's molecular basis and identify biomarkers.
Purpose of the Study:
- To explore genomic, transcriptomic, proteomic, and scRNA-seq data for insights into UC molecular mechanisms.
- To identify potential candidate biomarkers for UC.
- To investigate the causal relationship between DEGs and UC pathogenesis using Mendelian randomization.
Main Methods:
- Analysis of the GSE125527 scRNA-seq dataset for cell identification and DEG analysis.
- Mendelian randomization (MR) analysis using genome-wide association study (GWAS) data (ieu-a-32) with expression and protein quantitative trait loci (eQTL/pQTL) data.
- Integration of multi-omics data and in vitro/in vivo validation of candidate genes.
Main Results:
- Identification of 1,905 DEGs across 5 cell subtypes from 48,576 cells.
- FCN1 and ING4 identified as causally associated with UC through MR and eQTL/pQTL analysis.
- ING4 demonstrated reduced expression in UC tissues and LPS-treated cells, impacting NF-κB pathway and iNOS release, suggesting a role in inflammation.
Conclusions:
- ING4 is a candidate gene with a genetically supported link to UC, connecting immune variation to epithelial inflammation.
- ING4 serves as a promising candidate biomarker and potential therapeutic target for UC.
- Multi-omics data integration is crucial for understanding UC pathogenesis.
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