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Comparative gene expression profile of canine and human invariant Natural Killer T (iNKT) cells at single cell level [scRNA-seq]

ABSTRACT: Comparative gene expression profile of canine and human invariant Natural Killer T (iNKT) cells at single cell level [scRNA-seq]

PROVIDER: PRJNA954688 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR29767032.fastq.gz	Fastqsanger.gz
	SRR29767033.fastq.gz	Fastqsanger.gz
	SRR29767034.fastq.gz	Fastqsanger.gz
	SRR29767035.fastq.gz	Fastqsanger.gz
	SRR29767036.fastq.gz	Fastqsanger.gz

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Gene expression profile of canine Chimeric Antigen Receptor (CAR) Engineered invariant Natural Killer T (iNKT) cells

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Comparative gene expression profile of canine and human invariant Natural Killer T (iNKT) cells at single cell level [scRNA-seq]

Project description:We used single cell RNA sequencing (scRNA-seq) to characterize the heterogeneity of peripheral blood-derived canine iNKT cells relative to that of human iNKTs.

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Gene expression profile of canine Chimeric Antigen Receptor (CAR) Engineered invariant Natural Killer T (iNKT) cells

Project description:Gene expression profile of canine Chimeric Antigen Receptor (CAR) Engineered invariant Natural Killer T (iNKT) cells

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Gene Regulation by Histone Deacetylase 7 During Invariant Natural Killer T Cell Development

Project description:We have found that the signal-dependent chromatin modulator Histone Deacetylase 7 interacts with and corepresses the signature transcription factor of invariant natural Killer T (iNKT) cells, ZBTB16. This study was designed to determine the global effect on transcription of a gain-of-function mutant of HDAC7 during iNKT cell development and function. Va14/Ja18 T cell receptor transgenic thymocytes and splenocytes, which develop preferentially into iNKT cells, were profiled by RNA-seq with and without expression of a gain-of-functon HDAC7 transgene (HDAC7dP)

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Mitochondrial Metabolism is Essential for Invariant Natural Killer T Cell Development and Function

Project description:Conventional T cell fate and function are determined by coordination between cellular signaling and metabolism. Invariant natural killer T (iNKT) cells are a subset of “innate-like” pre-activated T cells whose dependence on mitochondrial metabolism remains elusive. Here, we showed that mature iNKT cells have reduced mitochondrial respiratory reserve and iNKT cell development was highly sensitive to perturbation of mitochondrial function. Mice with T cell-specific ablation of Rieske Iron-Sulphur protein (T-Uqcrfs1-/-), an essential subunit of mitochondrial complex III, had a dramatic reduction of iNKT cells in the thymus and periphery, but minimal effects on conventional T cell development. Residual iNKT cells in T-Uqcrfs1-/- mice retained ability to proliferate but exhibited increased apoptosis, decreased TCR signaling and impaired responses to TCR and IL-15 stimulation. Furthermore, knocking down RISP in mature iNKT cells diminished their cytokine production, correlating with reduced NFATC2 activity. Collectively, our data demonstrate a critical role for mitochondrial metabolism in iNKT cell development and activation outside of supporting bioenergetic demands.

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Critical role for very-long chain sphingolipids in invariant natural killer T cell development and homeostasis

Project description:The role of sphingolipids (SLs) in the immune system has come under increasing scrutiny recently due to the emerging contributions that these important membrane components play in regulating a variety of immunological processes. The acyl chain length of SLs appears particularly critical in determining SL function. Here we show a role for very-long acyl chain SLs (VLC-SLs) in invariant natural killer T (iNKT) cell maturation in the thymus and homeostasis in the liver. Ceramide synthase 2 (CerS2) null mice, which lack VLC-SLs, were susceptible to a hepatotropic strain of lymphocytic choriomeningitis virus, which is due to a reduction in the number of iNKT cells. Bone marrow chimera experiments indicated that hematopoietic-derived VLC-SLs are essential for maturation of iNKT cells in the thymus, whereas parenchymal-derived VLC-SLs are crucial for iNKT cell survival and maintenance in the liver. Our findings suggest a critical role for VLC-SL in iNKT cell physiology.

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Expression data from invariant natural killer T (iNKT) cells in spleen and adipose tissue

Project description:Adipose tissue iNKT cells have different functions than iNKT cells in the blood and other organs. We used microarrays to detail the global gene expression profiles that might underlie these phenotypic and functional differences in adipose iNKT cells compared to splenic iNKT cells.

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Single-cell Transcriptomics Reveal Different Maturation Stages and Sublineages Commitment of Human Thymic Invariant Natural Killer T Cells

Project description:Invariant natural killer T (iNKT) cells are a rare but heterogenous T-cell subset with potent cytotoxic and immunomodulatory properties. During thymic development, murine iNKT cells go through different maturation stages and differentiate into distinct sublineages, namely iNKT1, iNKT2, and iNKT17 cells. Recent reports indicate that iNKT2 cells display immature properties and also give rise to other subsets, whereas iNKT1 cells seem to be terminally differentiated. Whether human iNKT cells follow a similar differentiation model is still unknown. To define the maturation stages and to assess the sublineage commitment of human iNKT cells during thymic development, in the present study we performed single-cell RNA sequencing analysis on human iNKT cells isolated from thymocytes. We show that human iNKT cells displayed heterogeneity and our unsupervised analysis identified two clusters: a first cluster expressed an immature profile with high expression of genes that are important for iNKT cell development and proliferation, whereas a second cluster displayed a mature, terminally differentiated profile. Trajectory analysis suggested an ontological relationship between the two clusters. Evaluation of the expression of sublineage-defining gene sets revealed that the first cluster contained mainly cells with an iNKT2 signature, whereas the more differentiated one contained cells that resembled murine iNKT1 cells. Our data point to the existence of different maturation stages of human thymic iNKT cells and provide evidence for sublineage commitment of iNKT cells in the human thymus.

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Single-cell ATAC-seq of mouse thymus iNKT cells

Project description:Invariant natural killer T (iNKT) cells are innate-like T cells. Although remarkable advancements in the understanding of iNKT cell development have been made, the underlying molecular programs that guide iNKT cell lineages and the heterogeneity of iNKT subsets remain unclear.

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