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A unique epigenomic landscape defines CD8+ tissue-resident memory T cells [Perturb-seq]

ABSTRACT: A unique epigenomic landscape defines CD8+ tissue-resident memory T cells [Perturb-seq]

PROVIDER: PRJNA1057183 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR27353516_1.fastq.gz	Fastqsanger.gz
	SRR27353516_2.fastq.gz	Fastqsanger.gz
	SRR27353517_1.fastq.gz	Fastqsanger.gz
	SRR27353517_2.fastq.gz	Fastqsanger.gz
	SRR27353518_1.fastq.gz	Fastqsanger.gz

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A unique epigenomic landscape defines CD8+ tissue-resident memory T cells

Project description:Memory T cells provide rapid and long-term protection against infection and tumors. The memory CD8+ T cell repertoire contains phenotypically and transcriptionally heterogeneous subsets with specialized functions and recirculation patterns. While these T cell populations have been well characterized in terms of differentiation potential and function, the epigenetic changes underlying memory T cell fate determination and tissue-residency remain largely unexplored. Here, we examined the single-cell chromatin landscape of CD8+ T cells over the course of acute viral infection. We reveal an early bifurcation of memory precursors displaying distinct chromatin accessibility and define epigenetic trajectories that lead to a circulating (TCIRC) or tissue-resident memory T (TRM) cell fate. While TRM cells displayed a conserved epigenetic signature across organs, we demonstrate that these cells exhibit tissue-specific signatures and identify transcription factors that regulate TRM cell populations in a site-specific manner. Moreover, we demonstrate that TRM cells and exhausted T (TEX) cells are distinct epigenetic lineages that are distinguishable early in their differentiation. Together, these findings show that TRM cell development is accompanied by dynamic alterations in chromatin accessibility that direct a unique transcriptional program resulting in a tissue-adapted and functionally distinct T cell state.

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