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Human epigenetic and transcriptional T cell differentiation atlas for identifying functional T cell-specific enhancers.


ABSTRACT: The clinical benefit of T cell immunotherapies remains limited by incomplete understanding of T cell differentiation and dysfunction. We generated an epigenetic and transcriptional atlas of T cell differentiation from healthy humans that included exhausted CD8 T cells and applied this resource in three ways. First, we identified modules of gene expression and chromatin accessibility, revealing molecular coordination of differentiation after activation and between central memory and effector memory. Second, we applied this healthy molecular framework to three settings-a neoadjuvant anti-PD1 melanoma trial, a basal cell carcinoma scATAC-seq dataset, and autoimmune disease-associated SNPs-yielding insights into disease-specific biology. Third, we predicted genome-wide cis-regulatory elements

SUBMITTER: Giles JR 

PROVIDER: S-EPMC9214622 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature