Lu Haiyang, Liu Fangming, Li Yao, Wang Jiahui, Ma Mingyue, Gao Jie, Wang Xiangdong, Shen Zan, Wu Duojiao
Department of Oncology, Affiliated Sixth People's Hospital, Shanghai Jiaotong University, Shanghai, 200233, China.
Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Cell Biol Toxicol. 2021 Jun;37(3):367-378. doi: 10.1007/s10565-020-09546-0. Epub 2020 Jul 12.
CD8T cells play an important role in controlling infections and tumorigenesis in vivo. naïve CD8T cells exponentially expand and exert effector functions in response to TCR ligation. After antigen clearance, most effector CD8T cells (Teff) experience activation-induced cell death, only a small portion becomes long-lived memory T cells (Tmem). The cell-intrinsic mechanisms driving the differentiation need further understanding. Here we used combined transposase-accessible chromatin (ATAC-seq) technology and RNA-seq analysis to explore chromatin accessibility in CD8T cell subsets (naïve T cells, Teff, and Tmem). The data demonstrates different chromatin openness of CD8T cell states is associated with metabolic regulation and the high accessibility of upstream binding site SP1 emerged as critical transcription factor for both Teff and Tmem in fatty acid oxidation (FAO) and glycolysis. The different presence of accessible regions in CD8T cell subsets provides a novel perspective for understanding epigenetic mechanisms underlying T cell differentiation and related immune response.
CD8T细胞在体内控制感染和肿瘤发生过程中发挥着重要作用。初始CD8T细胞会呈指数级扩增，并在TCR连接时发挥效应功能。抗原清除后，大多数效应CD8T细胞（Teff）会经历活化诱导的细胞死亡，只有一小部分会成为长寿记忆T细胞（Tmem）。驱动这种分化的细胞内在机制尚需进一步了解。在此，我们使用了组合转座酶可及染色质（ATAC-seq）技术和RNA-seq分析，以探索CD8T细胞亚群（初始T细胞、Teff和Tmem）中的染色质可及性。数据表明，CD8T细胞不同状态下的染色质开放性与代谢调节相关，上游结合位点SP1的高可及性成为Teff和Tmem在脂肪酸氧化（FAO）和糖酵解过程中的关键转录因子。CD8T细胞亚群中可及区域的不同存在情况，为理解T细胞分化及相关免疫反应背后的表观遗传机制提供了新视角。
