气候变化领域集成服务门户(CCPortal): E2A-regulated epigenetic landscape promotes memory CD8 T cell differentiation

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DOI	10.1073/pnas.2013452118
	E2A-regulated epigenetic landscape promotes memory CD8 T cell differentiation
	Schauder D.M.; Shen J.; Chen Y.; Kasmani M.Y.; Kudek M.R.; Burns R.; Cui W.
发表日期	2021
ISSN	00278424
卷号	118 期号:16
英文摘要	During an acute viral infection, CD8 T cells encounter a myriad of antigenic and inflammatory signals of variable strength, which sets off individual T cells on their own differentiation trajectories. However, the developmental path for each of these cells will ultimately lead to one of only two potential outcomes after clearance of the infection-death or survival and development into memory CD8 T cells. How this cell fate decision is made remains incompletely understood. In this study, we explore the transcriptional changes during effector and memory CD8 T cell differentiation at the single-cell level. Using single-cell, transcriptome-derived gene regulatory network analysis, we identified two main groups of regulons that govern this differentiation process. These regulons function in concert with changes in the enhancer landscape to confer the establishment of the regulatory modules underlying the cell fate decision of CD8 T cells. Furthermore, we found that memory precursor effector cells maintain chromatin accessibility at enhancers for key memory-related genes and that these enhancers are highly enriched for E2A binding sites. Finally, we show that E2A directly regulates accessibility of enhancers of many memory-related genes and that its overexpression increases the frequency of memory precursor effector cells and accelerates memory cell formation while decreasing the frequency of short-lived effector cells. Overall, our results suggest that effector and memory CD8 T cell differentiation is largely regulated by two transcriptional circuits, with E2A serving as an important epigenetic regulator of the memory circuit. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	CD8 T cell; Epigenetics; LCMV; ScRNA-seq; T cell memory
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/179815
作者单位	Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI 53226, United States; Versiti Blood Research Institute, Milwaukee, WI 53226, United States; Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, United States
推荐引用方式 GB/T 7714	Schauder D.M.,Shen J.,Chen Y.,et al. E2A-regulated epigenetic landscape promotes memory CD8 T cell differentiation[J],2021,118(16).
APA	Schauder D.M..,Shen J..,Chen Y..,Kasmani M.Y..,Kudek M.R..,...&Cui W..(2021).E2A-regulated epigenetic landscape promotes memory CD8 T cell differentiation.Proceedings of the National Academy of Sciences of the United States of America,118(16).
MLA	Schauder D.M.,et al."E2A-regulated epigenetic landscape promotes memory CD8 T cell differentiation".Proceedings of the National Academy of Sciences of the United States of America 118.16(2021).