Morgan Duncan M, Shreffler Wayne G, Love J Christopher
Koch Institute for Integrative Cancer Research, MIT, Cambridge, Mass; Department of Chemical Engineering, MIT, Cambridge, Mass.
Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, Mass; Harvard Medical School and Massachusetts General Hospital, Boston, Mass; Food Allergy Center, Massachusetts General Hospital, Boston, Mass.
J Allergy Clin Immunol. 2022 Oct;150(4):748-755. doi: 10.1016/j.jaci.2022.08.010.
Single-cell RNA sequencing (scRNA-seq) offers the ability to resolve whole transcriptomes of single cells with substantial throughput, and it has revolutionized studies of gene expression. The transcriptional resolution available can uncover fine structures of biologic heterogeneity that are manifest among cell populations. Here, we review the applications of scRNA-seq to profile the phenotypes and clonotypes of CD4 T cells. First, we describe challenges inherent to scRNA-seq that are important for analysis of CD4 T cells, as well as the technical solutions that are emerging to address these challenges. We then consider major themes of the application of scRNA-seq to CD4 T cells, including investigation of CD4 T-cell heterogeneity in model systems, analysis of populations from the peripheral blood, and the profiling of tissue-resident populations. We place emphasis on capabilities unique to scRNA-seq, such as the ability to obtain paired T-cell receptor and transcriptome information from single T cells and the potential to elucidate interactions between CD4 T cells and other cells in their environment. Finally, we conclude by considering future areas of technologic advancement and innovation through which scRNA-seq may further shape our understanding of the roles of CD4 T cells in health and disease.
单细胞RNA测序（scRNA-seq）能够以高吞吐量解析单个细胞的全转录组，彻底改变了基因表达研究。现有的转录分辨率可以揭示细胞群体中生物学异质性的精细结构。在这里，我们综述了scRNA-seq在分析CD4 T细胞表型和克隆型方面的应用。首先，我们描述了scRNA-seq中对于分析CD4 T细胞很重要的固有挑战，以及为应对这些挑战而出现的技术解决方案。然后，我们考虑scRNA-seq应用于CD4 T细胞的主要主题，包括在模型系统中研究CD4 T细胞异质性、分析外周血中的细胞群体以及分析组织驻留细胞群体。我们着重介绍scRNA-seq独有的能力，比如从单个T细胞获取配对的T细胞受体和转录组信息的能力，以及阐明CD4 T细胞与其周围环境中其他细胞之间相互作用的潜力。最后，我们通过考虑技术进步和创新的未来领域来得出结论，scRNA-seq可能通过这些领域进一步塑造我们对CD4 T细胞在健康和疾病中的作用的理解。
