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Multiple subpopulations in medullary thymic epithelial cells are regulated by Aire with distinctive modes of gene regulations

ABSTRACT: Multiple subpopulations in medullary thymic epithelial cells are regulated by Aire with distinctive modes of gene regulations

PROVIDER: PRJNA844977 | ENA |

REPOSITORIES: ENA

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			Action	DRS
		Other
	SRR19525100.fastq.gz	Fastqsanger.gz
	SRR19525101.fastq.gz	Fastqsanger.gz
	SRR19525102.fastq.gz	Fastqsanger.gz
	SRR19552949.fastq.gz	Fastqsanger.gz

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Multiple subpopulations in medullary thymic epithelial cells are regulated by Aire with distinctive modes of gene regulations [CUT&Tag]

Project description:Aire, a transcriptional regulator whose defect results in the development of autoimmunity, controls the transcriptome in the bulk of medullary thymic epithelial cells (mTECs) including the genes for self-antigens. Mechanisms for this process, however, remained incompletely understood, especially regarding the effects of Aire in each subpopulation in mTECs. Here, we combined single-cell multi-omics (scMulti-seq) technologies by which gene expression and open chromatin were simultaneously profiled from the same cell and deeper single-cell sequencing by RamDA-seq which enabled profiling of the minimum dropout. scMulti-seq effectively demonstrated the subpopulations among mTECs associated with diverse transcription factor activities which are affected by Aire and developmental stages, while RamDA-seq revealed the different modes of gene regulations by Aire in different subpopulations. Aire is not only essential for the development of a specific population in which Aire induces a set of genes in a stochastic manner but also promotes the development of multiple subpopulations in which Aire enhances the expressions of genes in a coordinated manner. The former group of Aire-induced genes was characterized by enhanced H3K27me3 chromatin modifications and Aire seems to unleash these silenced genes by deactivating polycomb repressive complex 2 (PRC2). We also found unique gene signatures for the neonatal stage such as high expression of chemokines and expression of cortical TEC (cTEC)-like genes in TECs, which were Aire-independent. Our approach has illuminated the multilayered transcriptional control in mTECs governing the multiple subpopulations organizing the thymic microenvironment.

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Multiple subpopulations in medullary thymic epithelial cells are regulated by Aire with distinctive modes of gene regulations [bulkRNA-seq]

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Multiple subpopulations in medullary thymic epithelial cells are regulated by Aire with distinctive modes of gene regulations [scRNA-Seq and scATAC-Seq]

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Multiple subpopulations in medullary thymic epithelial cells are regulated by Aire with distinctive modes of gene regulations [bulkRNA-seq]

Project description:Multiple subpopulations in medullary thymic epithelial cells are regulated by Aire with distinctive modes of gene regulations [bulkRNA-seq]

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Multiple subpopulations in medullary thymic epithelial cells are regulated by Aire with distinctive modes of gene regulations [CUT&Tag]

Project description:Multiple subpopulations in medullary thymic epithelial cells are regulated by Aire with distinctive modes of gene regulations [CUT&Tag]

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Multiple subpopulations in medullary thymic epithelial cells are regulated by Aire with distinctive modes of gene regulations [deep single-cell RNA-seq]

Project description:Multiple subpopulations in medullary thymic epithelial cells are regulated by Aire with distinctive modes of gene regulations [deep single-cell RNA-seq]

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Multiple subpopulations in medullary thymic epithelial cells are regulated by Aire with distinctive modes of gene regulations [scRNA-Seq and scATAC-Seq]

Project description:Multiple subpopulations in medullary thymic epithelial cells are regulated by Aire with distinctive modes of gene regulations [scRNA-Seq and scATAC-Seq]

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Transcriptional regulation by Aire in medullary thymic epithelial cells revisited

Project description:The deficiency of Aire, a transcriptional regulator whose defect results in the development of autoimmunity, is associated with reduced expression of tissue-restricted self-Ags (TRAs) in medullary thymic epithelial cells (mTECs). Although the mechanisms underlying Aire-dependent expression of TRAs need to be explored, the physical identification of the target(s) of Aire has been hampered by the low and promiscuous expression of TRAs. We have tackled this issue by engineering mice with augmented Aire expression. Integration of the transcriptomic data from Aire-augmented and Aire-deficient mTECs revealed that a large proportion of so-called Aire-dependent genes, including those of TRAs, may not be direct transcriptional targets downstream of Aire. Rather, Aire induces TRA expression indirectly through controlling the heterogeneity of mTECs, as revealed by single-cell analyses. In contrast, Ccl25 emerged as a canonical target of Aire, and we verified this both in vitro and in vivo. Our approach has illuminated the Aire?s primary targets while distinguishing them from the secondary targets.

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Multiple subpopulations in medullary thymic epithelial cells are regulated by Aire with distinctive modes of gene regulations

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

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