Investigating the molecular mechanisms associated with ulcerative colitis through the application of single-cell combined spatial transcriptome sequencing

作者：Hua Huang, Jiaze Ma, Kang An, Tianwei Guo, Wei Sun, Yan Xu, Lijiang Ji · 发表于：Frontiers in Immunology · 年份：2025 · DOI：10.3389/fimmu.2025.1534768 · 被引用次数：6 · 研究领域：Single-cell and spatial transcriptomics、Inflammatory Bowel Disease、Neutrophil, Myeloperoxidase and Oxidative Mechanisms

Background Ulcerative colitis (UC) is a chronic inflammatory bowel disease marked by dysregulated immune responses, resulting in sustained inflammation and ulceration of the colonic and rectal mucosa. To elucidate the cellular subtypes and gene expression profiles implicated in the pathogenesis of UC, we utilized single-cell and spatial transcriptomic analyses. Methods We conducted an analysis of single-cell data to identify cell types involved in the pathogenesis of UC. Employing machine learning methodologies, we screened for key genes implicated in UC and validated these findings through spatial transcriptomics. Additionally, immunohistochemistry was performed on UC lesion samples to investigate the expression patterns of the identified key genes. In an animal model, we utilized immunofluorescence and western blotting to validate the expression of these genes in the affected intestinal segments. Results Our investigation identified specific monocyte subtypes associated with UC through a comprehensive analysis involving cell communication, Least Absolute Shrinkage and Selection Operator (LASSO), and Support Vector Machine (SVM) methodologies. Notably, two genes, G protein subunit gamma 5 ( GNG5 ) and tissue inhibitor of metalloproteinase 1 ( TIMP1 ), were identified as key regulators of UC development. Spatial transcriptomic indicated a downregulation of GNG5 expression in UC, whereas TIMP1 expression was upregulated. Furthermore, a significant correlation was detected betw...