Integration of single-cell transcriptome and genetic profiles reveals critical cell types and genes in inflammatory bowel disease
Chu, X.; Wang, S.; Wei, J.; Liu, H.; Yan, P.; Yang, Q.; Tang, Y.; Zhang, B.; Pang, E.
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The progression of inflammatory bowel disease (IBD), grouped into Crohns disease (CD) and ulcerative colitis (UC), involves multiple cell types and genes, but the identification of critical cell types and genes that contribute to intestinal inflammation remains challenging. By integrating human intestinal single-cell transcriptomic data from approximately 200 donors, we revealed the stromal cell-derived network in CD, enrichments of immune cells such as Th1 in CD, atypical B cells and Tfh in UC, AXL+SIGLEC6+ DCs and IgG+ Plasma B cells in both, and the association between SPP1+ Macrophages, FAP+ Fibroblasts and anti-TNF treatment resistance. We also investigated the gene expression characterization of enteric neurons. Additionally, by linking cell-type-specific transcriptional alterations with genetic profiles of disease risk and intestinal gene expression, we proposed B cells and cycling epithelial cells as critical cell types, and identified epithelial genes, such as GPX4, as associated with CD pathology. In summary, our study comprehensively characterized the single-cell landscape of human intestines in IBD and provided insights into cell types and genes highly involved in genetically determined CD pathology, thereby informing CD prediction, diagnosis, and the development of new therapeutic targets.
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