Abstract：
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.
摘要：
记忆CD8+T细胞池包含具有专门功能和再循环模式的表型和转录异质子集。这里,我们检查了从七个非淋巴器官分离的CD8+T细胞在四个不同的感染模型的表观遗传景观，与他们的循环T细胞对应物一起。使用单细胞转座酶可接近的染色质测序（scATAC-seq），我们发现组织常驻记忆T(TRM)细胞和循环记忆T(TCIRC)细胞沿着不同的表观遗传轨迹发育.我们确定了TRM细胞发育的器官特异性转录调节因子，包括FOSB,FOS,FOSL1和BACH2，并定义了跨器官TRM细胞常见的表观遗传特征。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，它们由TRM细胞不存在的TEX特异性表观遗传特征定义。一起,这一全面的数据资源表明,TRM细胞发育伴随着动态转录组改变和染色质可及性变化,这些变化指导组织适应和功能不同的T细胞状态.
