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Thymic epithelial cells co-opt lineage-defining transcription factors to eliminate autoreactive T cells

ABSTRACT: Thymic epithelial cells co-opt lineage-defining transcription factors to eliminate autoreactive T cells

PROVIDER: PRJNA800005 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR17713400_1.fastq.gz	Fastqsanger.gz
	SRR17713400_2.fastq.gz	Fastqsanger.gz
	SRR17713500_1.fastq.gz	Fastqsanger.gz
	SRR17713500_2.fastq.gz	Fastqsanger.gz
	SRR17713401_1.fastq.gz	Fastqsanger.gz

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Thymic epithelial cells co-opt lineage-defining transcription factors to eliminate autoreactive T cells [scATAC-seq]

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Project description:We profiled medullary thymic epithelial cell subsets and peripheral cell types by bulk RNA-seq to investigate mechanisms of T-cell tolerance.

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Thymic epithelial cells co-opt lineage-defining transcription factors to eliminate autoreactive T cells.

Project description:Medullary thymic epithelial cells (mTECs) ectopically express thousands of peripheral-tissue antigens (PTAs), which drive deletion or phenotypic diversion of self-reactive immature T cells during thymic differentiation. Failure of PTA expression causes multiorgan autoimmunity. By assaying chromatin accessibility in individual mTECs, we uncovered signatures of lineage-defining transcription factors (TFs) for skin, lung, liver, and intestinal cells-including Grhl, FoxA, FoxJ1, Hnf4, Sox8, and SpiB-in distinct mTEC subtypes. Transcriptomic and histologic analyses showed that these subtypes, which we collectively term mimetic cells, expressed PTAs in a biologically logical fashion, mirroring extra-thymic cell types while maintaining mTEC identity. Lineage-defining TFs bound to mimetic-cell open chromatin regions and were required for mimetic cell accumulation, whereas the tolerogenic factor Aire was partially and variably required. Expression of a model antigen in mimetic cells sufficed to induce cognate T cell tolerance. Thus, mTECs co-opt lineage-defining TFs to drive mimetic cell accumulation, PTA expression, and self-tolerance.

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Thymic epithelial cells co-opt lineage-defining transcription factors to eliminate autoreactive T cells

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

2022-06-16 | GSE194253 | GEO