不同的表观基因组景观是组织特异性记忆 T 细胞分化的基础

IF 25.5 1区 医学 Q1 IMMUNOLOGY Immunity Pub Date : 2024-07-22 DOI:10.1016/j.immuni.2024.06.014
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引用次数: 0

摘要

记忆性 CD8+ T 细胞池包含表型和转录异质性亚群,具有专门的功能和再循环模式。在这里,我们研究了在四种不同的感染模型中从七个非淋巴器官中分离出来的 CD8+ T 细胞的表观遗传学景观,以及它们的循环 T 细胞对应物。利用单细胞转座酶可获取染色质测序(scATAC-seq),我们发现组织驻留记忆T细胞(TRM)和循环记忆T细胞(TCIRC)沿着不同的表观遗传学轨迹发展。我们确定了TRM细胞发育的器官特异性转录调控因子,包括FOSB、FOS、FOSL1和BACH2,并定义了各器官TRM细胞共有的表观遗传学特征。最后,我们发现尽管末端TEX细胞与TRM细胞共享可访问的调控元件,但它们是由TRM细胞所没有的TEX特异性表观遗传特征所定义的。总之,这一全面的数据资源表明,TRM 细胞的发育伴随着动态转录组的改变和染色质可及性的改变,这些改变引导着组织适应性和功能上不同的 T 细胞状态。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Distinct epigenomic landscapes underlie tissue-specific memory T cell differentiation

The memory CD8+ T cell pool contains phenotypically and transcriptionally heterogeneous subsets with specialized functions and recirculation patterns. Here, we examined the epigenetic landscape of CD8+ T cells isolated from seven non-lymphoid organs across four distinct infection models, alongside their circulating T cell counterparts. Using single-cell transposase-accessible chromatin sequencing (scATAC-seq), we found that tissue-resident memory T (TRM) cells and circulating memory T (TCIRC) cells develop along distinct epigenetic trajectories. We identified organ-specific transcriptional regulators of TRM cell development, including FOSB, FOS, FOSL1, and BACH2, and defined an epigenetic signature common to TRM cells across organs. Finally, we found that although terminal TEX cells share accessible regulatory elements with TRM cells, they are defined by TEX-specific epigenetic features absent from TRM cells. Together, this comprehensive data resource shows that TRM cell development is accompanied by dynamic transcriptome alterations and chromatin accessibility changes that direct tissue-adapted and functionally distinct T cell states.

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来源期刊
Immunity
Immunity 医学-免疫学
CiteScore
49.40
自引率
2.20%
发文量
205
审稿时长
6 months
期刊介绍: Immunity is a publication that focuses on publishing significant advancements in research related to immunology. We encourage the submission of studies that offer groundbreaking immunological discoveries, whether at the molecular, cellular, or whole organism level. Topics of interest encompass a wide range, such as cancer, infectious diseases, neuroimmunology, autoimmune diseases, allergies, mucosal immunity, metabolic diseases, and homeostasis.
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