Department of Experimental Immunology, Immunology Frontier Research Center, Osaka University, Osaka, Japan; Department of Neurology, Graduate School of Medicine, Osaka University, Osaka, Japan; Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University, Osaka, Japan.
Department of Experimental Immunology, Immunology Frontier Research Center, Osaka University, Osaka, Japan; Faculty of Medicine, Osaka University, Osaka, Japan.
Cell Genom. 2024 Feb 14;4(2):100473. doi: 10.1016/j.xgen.2023.100473. Epub 2024 Jan 3.
CD4 T cells are key mediators of various autoimmune diseases; however, their role in disease progression remains unclear due to cellular heterogeneity. Here, we evaluated CD4 T cell subpopulations using decomposition-based transcriptome characterization and canonical clustering strategies. This approach identified 12 independent gene programs governing whole CD4 T cell heterogeneity, which can explain the ambiguity of canonical clustering. In addition, we performed a meta-analysis using public single-cell datasets of over 1.8 million peripheral CD4 T cells from 953 individuals by projecting cells onto the reference and cataloging cell frequency and qualitative alterations of the populations in 20 diseases. The analyses revealed that the 12 transcriptional programs were useful in characterizing each autoimmune disease and predicting its clinical status. Moreover, genetic variants associated with autoimmune diseases showed disease-specific enrichment within the 12 gene programs. The results collectively provide a landscape of single-cell transcriptomes of CD4 T cell subpopulations involved in autoimmune disease.
CD4 T 细胞是各种自身免疫性疾病的关键介质；然而，由于细胞异质性，其在疾病进展中的作用尚不清楚。在这里，我们使用基于分解的转录组特征描述和规范聚类策略来评估 CD4 T 细胞亚群。这种方法确定了 12 个独立的基因程序，这些程序控制着整个 CD4 T 细胞的异质性，可以解释规范聚类的模糊性。此外，我们通过将细胞投影到参考基因上，并对 953 个人的超过 180 万个外周 CD4 T 细胞的公共单细胞数据集进行荟萃分析，对 20 种疾病中的细胞频率和群体定性变化进行编目，对其进行了元分析。分析表明，这 12 个转录程序有助于描述每种自身免疫性疾病，并预测其临床状况。此外，与自身免疫性疾病相关的遗传变异在 12 个基因程序内显示出疾病特异性富集。这些结果共同提供了参与自身免疫性疾病的 CD4 T 细胞亚群的单细胞转录组图谱。
