1. Academic Validation
  2. Chromatin accessibility of CD8 T cell differentiation and metabolic regulation

Chromatin accessibility of CD8 T cell differentiation and metabolic regulation

  • Cell Biol Toxicol. 2021 Jun;37(3):367-378. doi: 10.1007/s10565-020-09546-0.
Haiyang Lu  # 1 Fangming Liu  # 2 Yao Li  # 3 Jiahui Wang 1 Mingyue Ma 2 Jie Gao 2 Xiangdong Wang 4 Zan Shen 5 Duojiao Wu 6
Affiliations

Affiliations

  • 1 Department of Oncology, Affiliated Sixth People's Hospital, Shanghai Jiaotong University, Shanghai, 200233, China.
  • 2 Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
  • 3 Department of Laboratory Animal Science, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
  • 4 Zhongshan Hospital, Fudan University, Shanghai, 200032, China. [email protected].
  • 5 Department of Oncology, Affiliated Sixth People's Hospital, Shanghai Jiaotong University, Shanghai, 200233, China. [email protected].
  • 6 Zhongshan Hospital, Fudan University, Shanghai, 200032, China. [email protected].
  • # Contributed equally.
Abstract

CD8+T cells play an important role in controlling infections and tumorigenesis in vivo. naïve CD8+T cells exponentially expand and exert effector functions in response to TCR ligation. After antigen clearance, most effector CD8+T 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 CD8+T cell subsets (naïve T cells, Teff, and Tmem). The data demonstrates different chromatin openness of CD8+T 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 CD8+T cell subsets provides a novel perspective for understanding epigenetic mechanisms underlying T cell differentiation and related immune response.

Keywords

CD8 T cell; Chromatin accessibility; Epigenetic regulation; Metabolism; SP1.

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