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Transcriptome and Chromatin Landscape of iNKT Cells are Shaped by Subset Differentiation and Antigen Exposure

ABSTRACT: Transcriptome and Chromatin Landscape of iNKT Cells are Shaped by Subset Differentiation and Antigen Exposure

PROVIDER: PRJNA678446 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12558000.fastq.gz	Fastqsanger.gz
	SRR12558100.fastq.gz	Fastqsanger.gz
	SRR12558200.fastq.gz	Fastqsanger.gz
	SRR12558300.fastq.gz	Fastqsanger.gz
	SRR12558400_1.fastq.gz	Fastqsanger.gz

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Transcriptome and Chromatin Landscape of iNKT cells are Shaped by Subset Differentiation and Antigen Exposure [ATAC-seq]

Project description:Invariant natural killer T cells (iNKT cells) differentiate into thymic NKT1, NKT2 and NKT17 subsets that are also peripheral. We determined if the gene programs associated with these thymic subsets were maintained in peripheral sites, the influence of tissue location, and if there were large-scale changes after antigen exposure. RNA-seq and ATAC-seq analyses showed that iNKT cells in any subset were similar, regardless of tissue location. Lung iNKT cell subsets shared the most distinct location-specific features, shared with other innate lymphocytes in the lung, possibly consistent with increased activation. After antigenic stimulation, iNKT cells underwent chromatin and transcription changes leading to two populations: one similar to follicular helper T cells and the other like NK cells. Phenotypic analysis indicated these changes were observed long-term, suggesting that iNKT cells gene programs are not fixed, but they are capable of chromatin remodeling after antigen to give rise to several new subsets.

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Project description:Transcriptome and Chromatin Landscape of iNKT Cells are Shaped by Subset Differentiation and Antigen Exposure [RNA-seq]

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Transcriptome and chromatin landscape of iNKT cells are shaped by subset differentiation and antigen exposure.

Project description:Invariant natural killer T cells (iNKT cells) differentiate into thymic and peripheral NKT1, NKT2 and NKT17 subsets. Here we use RNA-seq and ATAC-seq analyses and show iNKT subsets are similar, regardless of tissue location. Lung iNKT cell subsets possess the most distinct location-specific features, shared with other innate lymphocytes in the lung, possibly consistent with increased activation. Following antigenic stimulation, iNKT cells undergo chromatin and transcriptional changes delineating two populations: one similar to follicular helper T cells and the other NK or effector like. Phenotypic analysis indicates these changes are observed long-term, suggesting that iNKT cells gene programs are not fixed, but they are capable of chromatin remodeling after antigen to give rise to additional subsets.

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Project description:We identified a novel subset of iNKT cells, C2 iNKT cells, that circulate in the periphery. Correspondingly, we characterized the tissue-resident iNKT cell subset, C1 iNKT cells. The development and terminal maturation of C2 iNKT cells completely depended on the thymic epithelial IL-15 niche, whereas C1 iNKT cells were regulated also by local IL-15 niches in peripheral tissues. C2 iNKT cells expressed high levels of genes related to cytotoxicity and exhibited more NK cell-like features. Functionally, C2 iNKT cells regulated self-antigen expression for immune tolerance in the thymus and mediated cancer immunosurveillance in the periphery.

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