Characterization of CD44low CD62Llow CD8 T-cell subset
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ABSTRACT:
PROVIDER: PRJNA679044 | ENA |
REPOSITORIES: ENA
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Project description:To characterize CD44low CD62low CD8 T-cell subset (P4), we compared gene expression among four CD8 T-cell subsets. A hierarchical clustering of global gene expression showed that each subset of CD8 T-cells expresses a distinct gene profile. Genes expressed in activated T-cells were highly expressed in P4 cells compared to naive P1 cells. On the other hand, genes expressed in differentiated T-cells were less expressed in P4 cells compared to either central memory (P2) or effector/memory (P3) cells. These results indicate that P4 cells are in an activated, but pre-mature state and distinct from more differentiated subsets of CD8 T-cells such as central memory and effector/memory cells.
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Project description:CD8+ T cells provide protection from infection and tumor growth, and many current immunotherapies target molecules that enhance CD8+ T cell function and differentiation. The transcriptional programs orchestrating CD8+ T cell differentiation in response to infection has been described, but the changes in spatial chromatin organization accompanying effector and memory CD8+ T cell differentiation is unknown, despite research showing the importance of long-range chromatin interactions for transcriptional regulation in various cell types. Here, we studied how genome organization is integrated with CD8+ T cell differentiation and investigated the role of CTCF, a key factor that regulates genome organization through blocking or facilitating chromatin interactions, in regulating CD8+ T cell fates. We observed T cell subset-specific changes in chromatin organization and CTCF binding, and revealed weak-affinity CTCF binding is needed to promote terminal differentiation of CD8+ T cells by coordinating chromatin interactions that regulate transcriptional programs driving CD8+ T cell differentiation.
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