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Transcript-indexed ATAC-seq reveals paired single-cell T cell receptor identity and chromatin accessibility for precision immune profiling [Ensembl]

ABSTRACT: Transcript-indexed ATAC-seq reveals paired single-cell T cell receptor identity and chromatin accessibility for precision immune profiling [Ensembl]

PROVIDER: PRJNA419362 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6313420_1.fastq.gz	Fastqsanger.gz
	SRR6313420_2.fastq.gz	Fastqsanger.gz
	SRR6313421_1.fastq.gz	Fastqsanger.gz
	SRR6313421_2.fastq.gz	Fastqsanger.gz
	SRR6313412_1.fastq.gz	Fastqsanger.gz

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Transcript-indexed ATAC-seq reveals paired single-cell T cell receptor identity and chromatin accessibility for precision immune profiling

Project description:Transcript-indexed ATAC-seq reveals paired single-cell T cell receptor identity and chromatin accessibility for precision immune profiling

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Transcript-indexed ATAC-seq reveals paired single-cell T cell receptor identity and chromatin accessibility for precision immune profiling [Ensembl]

Project description:T cells create vast amounts of diversity in their T cell receptor (TCR) genes, enabling individual clones to recognize particular peptide-MHC ligands. Here we combine transposase accessible chromatin analysis and TCR sequencing (T-ATAC-seq) at the single-cell level. Using this approach, we identify epigenomic signatures in immortalized leukemic T cells, primary human T cells from healthy volunteers, and primary leukemic T cells from clinical patient samples. In healthy peripheral blood CD4+ T cells, we identify cis and trans regulators of naive and memory T cell states and find significant heterogeneity in surface marker-defined populations. In patients with cutaneous T cell lymphoma, we identify leukemic and non-leukemic regulatory pathways in cells from the same individual, which has been previously challenging. Thus, T-ATAC-seq is a new tool enabling analysis of epigenomic landscapes in clonal T cells and should be valuable for studies of T cell malignancy, immunity, and immunotherapy.

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Project description:T cells create vast amounts of diversity in the genes that encode their T cell receptors (TCRs), which enables individual clones to recognize specific peptide-major histocompatibility complex (MHC) ligands. Here we combined sequencing of the TCR-encoding genes with assay for transposase-accessible chromatin with sequencing (ATAC-seq) analysis at the single-cell level to provide information on the TCR specificity and epigenomic state of individual T cells. By using this approach, termed transcript-indexed ATAC-seq (T-ATAC-seq), we identified epigenomic signatures in immortalized leukemic T cells, primary human T cells from healthy volunteers and primary leukemic T cells from patient samples. In peripheral blood CD4+ T cells from healthy individuals, we identified cis and trans regulators of naive and memory T cell states and found substantial heterogeneity in surface-marker-defined T cell populations. In patients with a leukemic form of cutaneous T cell lymphoma, T-ATAC-seq enabled identification of leukemic and nonleukemic regulatory pathways in T cells from the same individual by allowing separation of the signals that arose from the malignant clone from the background T cell noise. Thus, T-ATAC-seq is a new tool that enables analysis of epigenomic landscapes in clonal T cells and should be valuable for studies of T cell malignancy, immunity and immunotherapy.

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