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Global transcriptional profiling reveals distinct functions of thymic stromal subsets and age-related changes during thymic involution

ABSTRACT: The thymic microenvironment is essential for proper differentiation and selection of thymocytes.Thymic involution in aged mice results in decreased T cell output and immune function. Here we use gene expression profiling of FACS sorted thymic stromal subsets to identify molecular mediators of thymocyte: stromal cell interactions, as well as gene expression changes thymic stromal subsets during early stages of thymic involution . We used microarrays to analyze gene expression differences between thymic stromal subsets from male C57BL/6J mice 1, 3, and 6 months of age. Thymic stromal subsets (cTEC, mTEClo, mTEChi, Sirpa-DC, Sirpa+DC, and fibroblasts) were isolated from two 1-, 3-, and 6- month old male C57BL/6J mice. After enzymatic digestion of the thymi, the stromal cells were FACS purified, and RNA was extracted, amplified, labeled and hybridized to Affymetrix mouse 430 2.0 arraysarrays. Raw data were uploaded to Gene Expression Commons for normalization. Both raw CEL and normalized datasets from the 36 samples are included. A model within Gene Expression Commons has been created for analyses/comparisons of these datasets, along with previously reported thymocyte subset datasets. The model within Gene Expression Commons thus contains 6 thymic stromal populations, each from mice 1, 3, and 6 months of age, with duplicates for each datset.

ORGANISM(S): Mus musculus

SUBMITTER: Lauren Ehrlich

PROVIDER: E-GEOD-56928 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Global transcriptional profiling reveals distinct functions of thymic stromal subsets and age-related changes during thymic involution

Project description:The thymic microenvironment is essential for proper differentiation and selection of thymocytes.Thymic involution in aged mice results in decreased T cell output and immune function. Here we use gene expression profiling of FACS sorted thymic stromal subsets to identify molecular mediators of thymocyte: stromal cell interactions, as well as gene expression changes thymic stromal subsets during early stages of thymic involution . We used microarrays to analyze gene expression differences between thymic stromal subsets from male C57BL/6J mice 1, 3, and 6 months of age.

2014-09-12 | GSE56928 | GEO

Qualitative changes in cortical thymic epithelial cells drive postpartum thymic regeneration.

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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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METTL3 governs thymocyte development and thymic involution by regulating ferroptosis

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Transcriptome analysis of murine thymocytes reveals age-associated changes in thymic gene expression

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2009-05-05 | E-GEOD-15945 | biostudies-arrayexpress

METTL3 governs thymocyte development and thymic involution by regulating ferroptosis

Project description:METTL3 governs thymocyte development and thymic involution by regulating ferroptosis

| PRJNA1130936 | ENA

Transcriptome analysis of murine thymocytes reveals age-associated changes in thymic gene expression

2009-05-05 | GSE15945 | GEO

Deletion of PKBalpha/Akt1 affects thymic development

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Dynamic Changes in Lymphocyte Populations Establish Zebrafish as a Thymic Involution Model

Project description:The thymus is the site of T lymphocyte development and T cell education to recognize foreign, but not self, antigens. B cells also reside and develop in the thymus, although their function(s) are less clear. During ‘thymic involution,’ a process of lymphoid atrophy and adipose replacement linked to sexual maturation, thymic cells decline. However, thymic B cells decrease far less than T cells, such that B cells comprise ~1% of neonatal thymocytes, but up to ~10% in adulthood in humans. All jawed vertebrates possess a thymus, and we and others have shown that zebrafish (Danio rerio) also have thymic B cells. Here, we investigated the precise identities of zebrafish thymic T and B cells and how they change with involution. We assessed the timing and specific details of zebrafish thymic involution using multiple lymphocyte-specific, fluorophore-labeled transgenic lines, quantifying changes in thymic lymphocytes pre- vs. post-involution. Our results prove that, as in humans, zebrafish thymic B cells increase relative to T cells post-involution. We also performed RNA sequencing (RNA-seq) on D. rerio thymic and marrow lymphocytes of four novel double-transgenic lines, identifying distinct populations of immature T and B cells. Collectively, this is the first comprehensive analysis of zebrafish thymic involution, demonstrating its similarity to human involution, and establishing the highly genetically-manipulatable zebrafish model as a template for involution studies.

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Role of AhR in thymocyte emigration in vivo

Project description:Over-activation of the aryl hydrocarbon receptor by TCDD in mice leads among other phenotypes to a severe thymic atrophy accompanied by immunosuppression. TCDD causes a block in thymocyte maturation and a preferential emigration of immature CD4-CD8- DN thymocytes (recent thymic emigrants) into the periphery. As part of this study gene expression profiles from DN thymocytes and thymic emigrants were generated from TCDD and solvent control mice Keywords: Affymetrix, TCDD, CD4-CD8- thymocytes, Thymus involution, thymic emigration, Ahr

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