Per-cell histone acetylation is associated with terminal differentiation in human T cells

作者全名："Yang, Cheng; Li, You; Hu, Yaqiu; Li, Qian; Lan, Yinghua; Li, Yongguo"

作者地址："[Yang, Cheng; Li, You; Hu, Yaqiu; Li, Qian; Li, Yongguo] Chongqing Med Univ, Affiliated Hosp 1, Dept Infect Dis, Chongqing 400016, Peoples R China; [Lan, Yinghua] Chongqing Med Univ, Affiliated Hosp 2, Inst Viral Hepatitis, Dept Infect Dis,Key Lab Mol Biol Infect Dis Minist, Chongqing 400010, Peoples R China"

通信作者："Li, YG (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Infect Dis, Chongqing 400016, Peoples R China.; Lan, YH (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Inst Viral Hepatitis, Dept Infect Dis,Key Lab Mol Biol Infect Dis Minist, Chongqing 400010, Peoples R China."

来源：CLINICAL EPIGENETICS

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001156944100001

JCR分区：Q1

影响因子：4.8

年份：2024

卷号：16

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Single-cell histone acetylation; Human T cell; TCF-1; Stemness; Terminal differentiation; C646

摘要："BackgroundEpigenetic remodeling at effector gene loci has been reported to be critical in regulating T cell differentiation and function. However, efforts to investigate underlying epigenetic mechanisms that control T cell behaviors have been largely hindered by very limited experimental tools, especially in humans.ResultsIn this study, we employed a flow cytometric assay to analyze histone acetylation at single-cell level in human T cells. The data showed that histone acetylation was increased during T cell activation. Among T cell subsets, terminally differentiated effector memory T (TEMRA) cells robustly producing effector cytokines were hyper-acetylated. Conversely, these TEMRA cells had lower expression levels of TCF-1, a key transcription factor for maintaining stem cell features. Pharmaceutical inhibition of histone acetylation using a small molecule C646 restrained the production of effector molecules, but retained stem cell-like properties in T cells after expansion.ConclusionsPer-cell histone acetylation is associated with terminal differentiation and poor stemness in human T cells. These observations suggest a new approach to enhance the stem cell-like properties of T cells and improve the efficacy of immunotherapy."

基金机构：National Natural Science Foundation of China

基金资助正文："We thank members of Li lab for their assistance in conducting this research, and Dr. Ying Yang (Department of Microbiology, Perelman School of Medicine at University of Pennsylvania) for helping to proof read of this manuscript."