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

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE103970 | GEO | 2018/07/23

REPOSITORIES: GEO

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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 [ChIP-seq]

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

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

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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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Project description:Large-scale single cell mapping of the thymic stroma identifies a new thymic epithelial cell lineage [ChIP-seq]

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

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Large-scale mapping of mammalian transcriptomes identifies conserved genes associated with different cell states.

Project description:Distinguishing cell states based only on gene expression data remains a challenging task. This is true even for analyses within a species. In cross-species comparisons, the results obtained by different groups have varied widely. Here, we integrate RNA-seq data from more than 40 cell and tissue types of four mammalian species to identify sets of associated genes as indicators for specific cell states in each species. We employ a statistical method, TROM, to identify both protein-coding and non-coding indicators. Next, we map the cell states within each species and also between species using these indicator genes. We recapitulate known phenotypic similarity between related cell and tissue types and reveal molecular basis for their similarity. We also report novel associations between several tissues and cell types with functional support. Moreover, our identified conserved associated genes are found to be a good resource for studying cell differentiation and reprogramming. Lastly, long non-coding RNAs can serve well as associated genes to indicate cell states. We further infer the biological functions of those non-coding associated genes based on their co-expressed protein-coding genes. This study demonstrates that combining statistical modeling with public RNA-seq data can be powerful for improving our understanding of cell identity control.

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