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RNA-sequencing of bulk CD19+ Thymic B cells from young (5 week) and aged (10-24 month) mice

ABSTRACT: RNA-sequencing of bulk CD19+ Thymic B cells from young (5 week) and aged (10-24 month) mice

PROVIDER: PRJNA419007 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6305410.fastq.gz	Fastqsanger.gz
	SRR6305411.fastq.gz	Fastqsanger.gz
	SRR6305412.fastq.gz	Fastqsanger.gz
	SRR6305413.fastq.gz	Fastqsanger.gz
	SRR6305404.fastq.gz	Fastqsanger.gz

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RNA-sequencing of bulk CD19+ Thymic B cells from young (5 week) and aged (10-24 month) mice

Project description:Thymic B cells have been recently shown the ability to be licensed to express Aire, a critical transcription factor involved in the expression of self-antigens in the thymus which are critical for clonal deletion of autoreactive T cells and maintenance of self-tolerance. Mutations in AIRE cause systemic autoimmunity in humans and autoimmunity with varying degrees of severity in different mouse strains. Thymic B cells have been studied in young animals, but studies of this population with age are lacking. Given the thymus undergoes age-associated atrophy in its stromal compartment, we hypothesized that aged thymic B cells may under go changes with age which may impact their ability to mediate clonal deletion of autoreactive T cells and may contribute to age-associated increases in autoimmune prevalence. By comparing the transcriptome of young and aged thymic B cells we find that Aire and transcriptional activators of Aire are signficantly decreased with age.

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Transcriptome analysis of thymic epithelial cells and thymic non-epithelial stromal cells from young, middle-aged and castrated middle-aged male mice

Project description:The thymus is primarily responsible for generating naïve, self-tolerant T cells from hematopoietic precursors. Thymic epithelial cells (TECs) together with other stromal cells create a specialized microenvironment which orchestrates the major selection processes for T cell development. Thymic function progressively deteriorates as part of the aging process, with a dramatic loss in TECs and T cell production, and this ultimately constrains the host immune repertoire. We have previously demonstrated the role of sex steroids in thymic involution in male mice, with surgical castration of middle-aged (9-12 month) male mice resulting in thymus regeneration, peaking around day 28. We have also demonstrated phenotypic alterations in TEC subsets within one week following castration that may contribute to this transient thymus regeneration effect. In this study, we aimed to examine genetic alterations in TEC and non-TEC stromal cell subsets (predominantly fibroblasts and endothelial cells) during age-related thymic involution (5-6 week old young adults compared to 9-12 month middle aged); and genetic changes in TEC and non-TEC at several timepoints following castration, to identify factors that may be involved in thymus regeneration.

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MicroRNA data in the hearts from young (8 week-old) and middle-aged (15 month-old) male mice

Project description:MicroRNAs have been reported to be involved in the regulation of cellular and organismal aging. However, little is known about the role of microRNAs in cardiac aging. We used microarrays to examine microRNA profiles in the hearts from young (8 week-old) and middle-aged (15 month-old) male mice.

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RNA-sequencing of bulk CD19+ Thymic B cells from young (3 month - 4 year) and old (42 - 61 years) humans

Project description:RNA-sequencing of bulk CD19+ Thymic B cells from young (3 month - 4 year) and old (42 - 61 years) humans

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RNA-sequencing of bulk CD19+ Thymic B cells from young (3 month - 4 year) and old (42 - 61 years) humans

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RNA-sequencing of bulk CD19+ Thymic B cells from mice and humans

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Project description:We report that a large percentage of thymic B cells undergo class switching intrathymically. Thymic B cell class switching requires cognate T-B interaction. To determine whether B cell specificity was also important for thymic B cell class-switching, we sorted class-switched thymic B cells (CD19+B220+IgM-IgD-), unswitched B cells (CD19+B220+IgM+IgD+) and bulk splenic B cells in 3H9 heavy chain-fixed mice and performed high throughput sequencing analysis of the light chain of these populations. Results of this analysis indicated that class-switched thymic B cells have a distinct repertoire compared with unswitched thymic B cells and splenic B cells. Further reactivity tests indicated that a large part of BCRs enriched in class-switched thymic B cells are autoreactive. These data suggest that autoreactive B cells are selected into class-switched population and expanded in the thymus. Light chain repertoire profiles of class-switched thymic B cells, unswithced thymic B cells and splenic B cells from 3H9 mice were generated by deep sequencing.

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BCR repertoire analyis of class-switched and non-switched thymic B cells

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