生物
表观遗传学
染色质
效应器
细胞分化
重编程
细胞生物学
增强子
清脆的
转录因子
细胞
遗传学
基因
作者
Qiao Liu,Wei Dong,Rong Liu,Luming Xu,Ling Ran,Ziying Xie,Shun� Lei,Xingxing Su,Zhengliang Yue,Dan Xiong,Lisha Wang,Shuqiong Wen,Yan Zhang,Jianjun Hu,Chenxi Qin,Yongchang Chen,Bo Zhu,Xiangyu Chen,Xia Wu,Lifan Xu
标识
DOI:10.1093/procel/pwaf003
摘要
Abstract Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
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