Identification of Novel Population-Specific Cell Subsets in Chinese Ulcerative Colitis Patients Using Single-Cell RNA Sequencing

BACKGROUND & AIMS: Genome-wide association studies (GWAS) and transcriptome analyses have been performed to better understand the pathogenesis of ulcerative colitis (UC). However, current studies mainly focus on European ancestry, highlighting a great need to identify the key genes, pathways and cell types in colonic mucosal cells of adult UC patients from other ancestries. Here we aimed to identify key genes and cell types in colonic mucosal of UC. METHODS: We performed Single-cell RNA sequencing (scRNA-seq) analysis of 12 colon biopsies of UC patients and healthy controls from Chinese Han ancestry. RESULTS: Two novel plasma subsets were identified. Five epithelial/stromal and three immune cell subsets show significant difference in abundance between inflamed and non-inflamed samples. In general, UC risk genes show consistent expression alteration in both Immune cells of inflamed and non-inflamed tissues. As one of the exceptions, IgA defection, marking the signal of immune dysfunction, is specific to the inflamed area. Moreover, Th17 derived activation was observed in both epithelial cell lineage and immune cell lineage of UC patients as compared to controls, suggesting a systemic change of immune activities driven by Th17. The UC risk genes show enrichment in progenitors, glial cells and immune cells, and drug-target genes are differentially expressed in antigen presenting cells. CONCLUSIONS: Our work identifies novel population-specific plasma cell molecular signatures of UC. The transcriptional signature of UC is shared in immune cells from both inflamed and non-inflamed tissues, whereas the transcriptional response to disease is a local effect only in inflamed epithelial/stromal cells.

Automated summary

This study identified two novel plasma cell subsets in colon mucosa of UC patients through single-cell RNA sequencing analysis, as well as significant differences in five epithelial/stromal and three immune cell subsets between inflamed and non-inflamed samples. UC risk genes show consistent expression alteration in immune cells, while specific immune dysfunction signals like IgA defect are observed only in the inflamed area. Th17-driven immune activities changes were observed in both epithelial and immune cell lineages of UC patients compared to controls. The enriched UC risk genes in progenitors, glial cells, and immune cells, along with differential expression of drug-target genes in antigen presenting cells, were also noted.