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Mus musculus strain:C57BL/6

ABSTRACT: RNA-seq analysis of transit-amplifying Aire+ mTECs

PROVIDER: PRJDB9868 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	DRR228448.fastq.gz	Fastqsanger.gz
	DRR228449.fastq.gz	Fastqsanger.gz
	DRR228450.fastq.gz	Fastqsanger.gz
	DRR228451.fastq.gz	Fastqsanger.gz
	DRR228452.fastq.gz	Fastqsanger.gz

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Single cell sequencing defines a branched progenitor population of stable medullary thymic epithelial cells

Project description:Medullary thymic epithelial cells (mTECs) play a critical role in central immune tolerance by mediating negative selection of autoreactive T cells through the collective expression of the peripheral self-antigen compartment, including tissue-specific antigens (TSAs). Recent work has shown that gene expression patterns within the mTEC compartment are remarkably heterogenous and include multiple differentiated cell states. To further define mTEC development and medullary epithelial lineage relationships, we combined lineage tracing and recovery from transient in vivo mTEC ablation with single cell RNA-sequencing in Mus musculus. The combination of bioinformatic and experimental approaches revealed a non-stem transit-amplifying population of cycling mTECs that preceded Aire expression. Based on our findings, we propose a branching model of mTEC development wherein a heterogeneous pool of transit-amplifying cells gives rise to Aire- and Ccl21a-expressing mTEC subsets. We further use experimental techniques to show that within the Aire-expressing developmental branch, TSA expression peaked as Aire expression decreased, implying Aire expression must be established before TSA expression can occur. Collectively, these data provide a higher order roadmap of mTEC development and demonstrate the power of combinatorial approaches leveraging both in vivo models and high-dimensional datasets.

2020-11-24 | GSE137699 | GEO

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Project description:RNA-seq analysis of transit amplifying mTEC in reaggregation thymic organ culture

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Aire regulates chromatin looping by evicting CTCF from domain boundaries and favoring accumulation of cohesin on super-enhancers [RNA-seq]

Project description:RNA-seq analysis of Aire+/+ and Aire-/- mTECs with or without deletion of STAG2 (SA-2).

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Characterizing phenotypic data of Peromyscus leucopus compared to C57BL/6J Mus musculus and diversity outbred (DO) Mus musculus.

Project description:Translational research is commonly performed in the C57B6/J mouse strain, chosen for its genetic homogeneity and phenotypic uniformity. Here, we evaluate the suitability of the white-footed deer mouse (Peromyscus leucopus) as a model organism for aging research, offering a comparative analysis against C57B6/J and diversity outbred (DO) Mus musculus strains. Our study includes comparisons of body composition, skeletal muscle function, and cardiovascular parameters, shedding light on potential applications and limitations of P. leucopus in aging studies. Notably, P. leucopus exhibits distinct body composition characteristics, emphasizing reduced muscle force exertion and a unique metabolism, particularly in fat mass. Cardiovascular assessments showed changes in arterial stiffness, challenging conventional assumptions and highlighting the need for a nuanced interpretation of aging-related phenotypes. Our study also highlights inherent challenges associated with maintaining and phenotyping P. leucopus cohorts. Behavioral considerations, including anxiety-induced responses during handling and phenotyping assessment, pose obstacles in acquiring meaningful data. Moreover, the unique anatomy of P. leucopus necessitates careful adaptation of protocols designed for Mus musculus. While showcasing potential benefits, further extensive analyses across broader age ranges and larger cohorts are necessary to establish the reliability of P. leucopus as a robust and translatable model for aging studies.

| S-EPMC11335981 | biostudies-literature

Mus musculus

Project description:Single cell analysis of transit-amplifying thymic epithelial cells

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Identification of a novel Aire-regulating cis-regulatory element using H3K27ac ChIP-seq

Project description:Thymic central tolerance is essential to preventing autoimmunity. In medullary thymic epithelial cells (mTECs), the Autoimmune regulator (Aire) gene plays an essential role in this process by driving the expression of a diverse set of tissue-specific antigens (TSAs), which are presented and help tolerize self-reactive thymocytes. Interestingly, Aire has a highly tissue-restricted pattern of expression, with only mTECs and peripheral extrathymic Aire-expressing cells (eTACs) known to express detectable levels in adults. Despite this high level of tissue specificity, the cis-regulatory elements that control Aire expression have remained obscure. We used sequence conservation analysis and ChIP-seq against the enhancer-associated histone mark H3K27ac to identify a candidate Aire cis-regulatory element. There is enrichment of H3K27ac near this element, ACNS1, in mTECs and the element also has characteristics of being NF-ÎºB-responsive. Finally, we find that this element is essential for Aire expression in vivo and necessary to prevent spontaneous autoimmunity, reflecting the importance of this regulatory DNA element in promoting immune tolerance. Two experimental groups (GFP neg mTECs and GFP pos mTECs), each with three samples, and one control sample (D10 Th2 cells).

2015-10-23 | E-GEOD-74257 | biostudies-arrayexpress

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Project description:Expression data from WT and Aire deficient mTECs

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Aire regulates chromatin looping by evicting CTCF from domain boundaries and favoring accumulation of cohesin on super-enhancers [Hi-C]

Project description:Hi-C analysis of Aire+/+ and Aire-/- mTECs

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Project description:To gain insights into the difference in transcriptional programs regulated by Fezf2, Aire and Chd4, we performed RNA sequencing (RNA-seq) of mTECs from Fezf2-deficient, Aire-deficient and Chd4-deficient mice.

2020-02-07 | GSE144877 | GEO

Aire regulates chromatin looping by evicting CTCF from domain boundaries and favoring accumulation of cohesin on super-enhancers [ChIP-seq]

Project description:ChIP-seq for proteins involved in Aire's functioning in Aire+/+ and Aire-/- mTECs

2021-07-30 | GSE180934 | GEO