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Large-scale single cell mapping of the thymic stroma identifies a new thymic epithelial cell lineage

ABSTRACT: Large-scale single cell mapping of the thymic stroma identifies a new thymic epithelial cell lineage

PROVIDER: PRJNA407802 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6048950_1.fastq.gz	Fastqsanger.gz
	SRR6048950_2.fastq.gz	Fastqsanger.gz
	SRR6048960_1.fastq.gz	Fastqsanger.gz
	SRR6048960_2.fastq.gz	Fastqsanger.gz
	SRR6048970_1.fastq.gz	Fastqsanger.gz

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Large-scale single cell mapping of the thymic stroma identifies a new thymic epithelial cell lineage [ATAC-seq]

Project description:T cell development and selection is orchestrated in the thymus by a specialized niche of diverse stromal populations. By transcriptional single cell sorting, we de novo characterize the entire stromal compartment of the thymus. We identified dozens of cell states within the thymic stroma, with thymic epithelial cells (TEC) showing the highest degree of heterogeneity. Our analysis highlights four major medullary TEC (mTEC I-IV) populations, with distinct molecular functions, epigenetic landscapes and lineage regulators. Specifically, mTEC-IV constitutes a new and highly divergent TEC lineage with molecular characteristics of the gut chemosensory epithelial tuft cells. Mice deficient of Pou2f3, a tuft cells master regulator, resulted in complete and specific depletion of mTEC-IV, without affecting other TEC populations. Overall, our study comprehensively defines all stroma cells in the thymus and identifies a new TEC lineage associated with chemosensory properties that may potentially link the adaptive immune system to environmental and neurological signals.

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Large-scale single cell mapping of the thymic stroma identifies a new thymic epithelial cell lineage [ATAC-seq]

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Large-scale single cell mapping of the thymic stroma identifies a new thymic epithelial cell lineage

Project description:This SuperSeries is composed of the SubSeries listed below.

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Dynamic changes of nonepithelial thymic stroma during thymus organogenesis

Project description:The thymic stroma provides the microenvironment for T cell lineage commitment, development, maturation, and repertoire selection. While the thymic epithelial cell (TEC) compartment is relatively well characterised, a comparably detailed analysis of the non-TEC stromal compartment including the endothelial cells and fibroblasts is currently lacking. Here, we probe the composition of thymic mesenchymal cells and their dynamic change during thymus organogenesis. Using a single cell transcriptomic approach, we identify previously unappreciated heterogeneity within the non-TEC stromal compartment and demonstrate dynamic shifts within non-TEC stromal cell populations over thymic development. We then use a compound heterozygous model (Tbx1+/-Crkl+/-) for 22q11.2DS syndrome to show that significant reductions of multiple mesenchymal subpopulations associated with functional defects and accelerated aging are associated with the thymic hypoplasia observed in this condition. Thus, we provided a comprehensive picture of non-TEC thymic stromal development and their functional defects in a disease model of thymic hypoplasia.

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