Transcriptome diversity in human medullary thymic epithelial cells - RNAseq
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA832751 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The induction of central T-cell tolerance in the thymus depends on the presentation of peripheral self-epitopes by medullary thymic epithelial cells (mTECs), enabled by a process known as promiscuous gene expression (pGE). Transcriptome diversity generated during pGE has many contributors, including non-canonical transcription initiation, alternative splicing and expression of endogenous retroelements (EREs). However, their significance and regulation are poorly understood in the healthy human thymus. Here, we mapped the expression of genome-wide transcripts in immature and mature human mTECs using high-throughput 5'Cap and RNA sequencing. Overall, 96\% of protein coding genes were represented across five human mTEC samples, with mature mTECs showing increased rates of global transcript mis-initiation. Both mTEC populations have increased splicing entropy, which appears to be driven by expression of peripheral splicing factors. Furthermore, EREs enriched in long terminal repeat retrotransposons are up-regulated during mTEC maturation and enriched in genomic proximity to differentially expressed genes. We provide an interactive interface to explore the transcriptome diversity we uncovered at http://transcriptomediversity.cshl.edu/. Our findings represent an important first step towards the generation of a comprehensive map of transcriptome diversity in the healthy human thymus. Ultimately, a complete map of thymic expression diversity will allow for the identification of epitopes that contribute to the pathogenesis of auto-immunity and that drive immune recognition of tumor antigens.
2022-04-30 | GSE201719 | GEO
Project description:Transcriptome diversity in human medullary thymic epithelial cells
| PRJNA832748 | ENA
Project description:The induction of central T-cell tolerance in the thymus depends on the presentation of peripheral self-epitopes by medullary thymic epithelial cells (mTECs), enabled by a process known as promiscuous gene expression (pGE). Transcriptome diversity generated during pGE has many contributors, including non-canonical transcription initiation, alternative splicing and expression of endogenous retroelements (EREs). However, their significance and regulation are poorly understood in the healthy human thymus. Here, we mapped the expression of genome-wide transcripts in immature and mature human mTECs using high-throughput 5'Cap and RNA sequencing. Overall, 96% of protein coding genes were represented across five human mTEC samples, with mature mTECs showing increased rates of global transcript mis-initiation. Both mTEC populations have increased splicing entropy, which appears to be driven by expression of peripheral splicing factors. Furthermore, EREs enriched in long terminal repeat retrotransposons are up-regulated during mTEC maturation and enriched in genomic proximity to differentially expressed genes. We provide an interactive interface to explore the transcriptome diversity we uncovered at http://transcriptomediversity.cshl.edu/. Our findings represent an important first step towards the generation of a comprehensive map of transcriptome diversity in the healthy human thymus. Ultimately, a complete map of thymic expression diversity will allow for the identification of epitopes that contribute to the pathogenesis of auto-immunity and that drive immune recognition of tumor antigens.
2022-04-30 | GSE201718 | GEO
Project description:Transcriptome diversity in human medullary thymic epithelial cells - 5'Cap sequencing
| PRJNA832752 | ENA
Project description:Thymic epithelial cells govern thymic T lymphocyte differentiation and selection. Medullary TECs (mTECs) facilitate the negative selection of self-reactive thymocytes and the differentiation of FOXP3+ regulatory T cells. Medullary TECs are also distinctive for their “promiscuous” gene expression, transcribing thousands of peripheral tissue genes (PTG) that are otherwise only expressed highly in one or two other organs. Much of this PTG expression by mTECs is controlled by the autoimmune regulator, AIRE. To probe the mechanism by which KAT7 promotes AIRE function, we performed ATAC-seq to compare chromatin accessibility in MHCII-high medullary thymic epithelial cells from Kat7-knockout and wildtype mice.
2021-12-21 | GSE188868 | GEO
Project description:We have found that Cdx1 can promote ectopic gene expression in thymic epithelial cells. We isolated MHCIIhi CD80hi medullary thymic epithelial cells from Cdx1-/- and Cdx1+/+ and compare gene expression between the two subsets, also in the context of Cdx1-mediated changes in intestinal epithelial cells.
2018-05-01 | GSE68880 | GEO
Project description:10x sequencing of TSPAN8+, GP2+ or Unselected medullary thymic epithelial cells (mTEC) isolated from female C57BL/6, BALB/c, and C57BL/6 x BALB/c F1 mice with the intent to identify co-expression patterns in promiscuously expressed genes in individual mTEC.
2019-10-17 | E-MTAB-8105 | biostudies-arrayexpress
Project description:We compared gene expression profiles of lymphotoxin alpha- and lymphtoxin beta receptor-deficient thymic medullary epithelial cells with their wild-type littermates, as well as with Aire-deficient and wild-type littermates. This was done in order to determine whether there was overlap in the effects of lymphotoxin and aire. Keywords: genetic modification
2007-10-23 | GSE8563 | GEO
Project description:The oligo microarrays were used to determine mRNA expression profiles of medullary thymic epithelial cells (mTECs) isolated from thymus of pre-diabetic NOD mice.
2012-08-11 | E-MEXP-3358 | biostudies-arrayexpress
Project description:Medullary thymic epithelial cells play essential role for induction of central self-tolerance by facilitating negative selection of self-reactive thymocytes and the generation of Foxp3+ regulatory T cells. Although studies highlighted the non-canonical NFκB pathway as the key regulator of mTEC development, comprehensive understanding of the molecular pathways regulating this process still remains incomplete. The aim of this study was to analyze the impact of Histone deacetylase 3 (HDAC3), which is highly expressed by mTECs, on mTEC development and function. We used Affymetrix mouse 1ST arrays to analyze the impact of the Hdac3 gene on the gene expression profile of MHC-II medullary thymic epithelial cells
2016-04-01 | GSE78283 | GEO