Transcription profiling of thymic epithelial cells from C57BL/6 and AIRE knockout mice.
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Ratanmani Joshi
PROVIDER: E-GEOD-2515 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Promiscuous gene expression (pGE) of numerous self-antigens in thymic epithelial cells (TEC) enables the elimination of self-reactive T cells. The autoimmune regulator (Aire) is the only known molecular determinant driving pGE in the thymus but the existence of Aire-independent mechanisms has been inferred. Here, we analyzed the poly(A)+ transcriptome of TEC populations by RNA-sequencing (RNA-seq) in order to reveal differential features of Aire-induced vs. –independent pGE. We report an unanticipated effect of Aire deletion on the proliferation and differentiation of cortical TEC. Moreover, the RNA-seq data reveal the breath of Aire-induced and –independent pGE in medullary TEC (mTEC) subsets and the extent of thymic peripheral tissue representation. The results suggest that Aire-induced promiscuously expressed transcripts affect several functions with far reaching biological consequences in mTEC. High-throughput characterization of TEC transcriptomes will enable progress in understanding TEC biology and the establishment of self-tolerance. The mRNA profiles of cTEC, mTEClo and mTEChi from 6-8 week-old wild type (WT) and Aire-/- (KO) mice were generated by RNA-sequencing using Illumina HiSeq2000.
2015-05-19 | E-GEOD-65617 | biostudies-arrayexpress
Project description:Promiscuous gene expression (pGE) of numerous self-antigens in thymic epithelial cells (TEC) enables the elimination of self-reactive T cells. The autoimmune regulator (Aire) is the only known molecular determinant driving pGE in the thymus but the existence of Aire-independent mechanisms has been inferred. Here, we analyzed the poly(A)+ transcriptome of TEC populations by RNA-sequencing (RNA-seq) in order to reveal differential features of Aire-induced vs. –independent pGE. We report an unanticipated effect of Aire deletion on the proliferation and differentiation of cortical TEC. Moreover, the RNA-seq data reveal the breath of Aire-induced and –independent pGE in medullary TEC (mTEC) subsets and the extent of thymic peripheral tissue representation. The results suggest that Aire-induced promiscuously expressed transcripts affect several functions with far reaching biological consequences in mTEC. High-throughput characterization of TEC transcriptomes will enable progress in understanding TEC biology and the establishment of self-tolerance.
2015-05-19 | GSE65617 | GEO
Project description:TEC (B6 vs Aire KO). Thymic epithelial cells from B6 strain and AIRE KO are compared. Keywords: repeat sample
2006-04-11 | GSE2515 | GEO
Project description:The autoimmune regulator, AIRE, induces the transcription of thousands of peripheral tissue genes (PTGs) in thymic epithelial cells (TECs) to mediate immunological tolerance. The chromatin state required for optimal AIRE function in TECs and how this state is induced remains unclear. Using RNA-seq and ATAC-seq, we tested the role of the histone acetyltransferase, KAT7 (also known as HBO1 or MYST2), which is essential for acetylation of histone 3 lysine 14 (H3K14), in TEC differentiation, AIRE-mediated PTG expression and thymic tolerance. We find that KAT7 is required for optimal expansion of medullary TEC and has a major role in the expression of AIRE-dependent PTGs, associated with enhanced chromatin accessibility at these gene loci in TECs. Mice with TEC-specific Kat7 deletion develop organ-specific autoimmunity with features resembling those observed in Aire-deficient mice. These findings highlight critical roles for KAT7-mediated acetylation in promoting a chromatin state at PTG loci that enables AIRE function and the establishment of immunological tolerance.
2021-12-21 | GSE188871 | GEO
Project description:T cell differentiation is governed by interactions with thymic epithelial cells (TECs) and defects in this process undermine immune function and tolerance. To uncover new strategies to restore thymic function and adaptive immunity in immunodeficiency, we sought to determine the molecular mechanisms that control life and death decisions in TEC. We created a mouse model which specifically deleted the pro-survival gene Mcl1 in TEC. We found that while BCL-2 and BCL-XL were dispensable for TEC homeostasis, MCL-1 deficiency impacted on TEC as early as E15.5, resulting in early thymic atrophy and T cell lymphopenia, with near complete loss of thymic tissue by 2 months of age. MCL-1 was not necessary for TEC differentiation but was continually required for the survival of medullary TEC, including autoimmune regulator (AIRE) expressing TECs and the maintenance of overall thymic architecture. To understand the molecular mechanisms in more detail, RNA-seq profiling was undertaken of cortical and medullary thymic epithelial cells (cTECs and mTECs) from wildtype and knockout mice.
2017-09-25 | GSE102227 | GEO
Project description:Aire in medullary thymic epithelial cells plays an essential role in the negative selection through expression of broad arrays of tissue-restricted antigens. We asked whether Aire could also activate the expression of tissue-restricted antigens in cortical thymic epithelial cells. We established a semi-knockin strain of NOD-background mice expressing Aire under control of the promoter of β5t, a thymoproteasome expressed exclusively in the cortex. We extracted RNA from cortical thymic epithelial cells ectopically expressing Aire and hybridization was performed on Affymetrix. microarrays.
2015-08-03 | E-GEOD-70326 | biostudies-arrayexpress
Project description:The goal of the study was to sequence mRNA expression from sorted medullary thymic epithelial cell (mTEC) subsets in inducible Aire-CreERT2.R26-Stopfl-tdTomato lineage tracing mice after a pulse chase. Four cell subsets were sorted 7 days after a single 2mg pulse of tamoxifen administered by oral gavage. 4 biological replicates (1,2,3,4) were collected derived from 12 pooled thymi per replicate. From the DAPI-;CD45-;EpCAM+ TEC pool, cells were sorted as: pre-Aire (MHCIIlo;RFP-), early-Aire (MHCIIhi;RFP-), late-Aire (MHCIIhi;RFP+), and post-Aire (MHCIIlo;RFP+). The data were used to identify differentially expressed genes across the four mTEC subsets to examine mTEC heterogeneity and identify novel mTEC subpopulations.
2018-05-19 | GSE114651 | GEO
Project description:Aire in medullary thymic epithelial cells plays an essential role in the negative selection through expression of broad arrays of tissue-restricted antigens. We asked whether Aire could also activate the expression of tissue-restricted antigens in cortical thymic epithelial cells.
2015-08-03 | GSE70326 | GEO
Project description:Microarray analysis of AIRE regulated gene expression has been performed extensively in studies using the thymi of different mouse strains, but to date, has only been rarely performed using human model systems, and critically, not yet with a human thymic model. We have generated a Flp-In host cell line variant of the TEC 1A3 human thymic epithelial cell line and subsequently used site-specific recombination to generate a variant that stably expresses recombinant AIRE. We used microarray analysis to determine the transcription expression profiles of these two variants and determine the repertoire of AIRE regulated gene expression in a human thymic model system. The aim of the present study is to use microarray analysis to identify the repertoire of AIRE regulated genes within a human model system, and to validate this model as an appropriate human model system for the study of the molecular function of AIRE
2018-06-01 | GSE35244 | GEO
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.
2021-10-13 | GSE155331 | GEO