Transcriptome sequencing of Wild-type and psmb11-/- thymic epithelial cells
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE71268 | GEO | 2018/07/20
REPOSITORIES: GEO
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Project description:Purpose: Cortical thymic epithelial cells (cTECs) contain a unique type of proteasomes, thymoproteasomes. Indirect evidence suggests that the key role of PSMB11, a catalytic subunit of thymoproteasomes specific to cTECs, is to generate a unique repertoire of MHC I peptides. Notably, PSMB11-deficient mice display defective development of CD8 thymocytes. The objective of this study was to characterize the impact of PSMB11 on cTECs and thymocyte development. Since different types of proteasomes have non-redundant effects on gene expression, we hypothesized that thymoproteasomes should have a distinct impact on the transcriptome and thereby the function of cTECs. Results: We report that PSMB11 in cortical thymic epithelial cells has dramatic effects on cTECs on both CD4 and CD8 thymocyte populations. PSMB11 modulates the expression of 850 genes in cTECs, 582 in CD4 thymocytes and 284 in CD8 thymocytes. PSMB11-regulated cTEC genes are involved mainly in cell-cell adhesion, extracellular matric organization and thymocyte chemotaxis. PSMB11-deficient cTECs acquire features of mTECs and perturb thymocyte development. Deletion of PSMB11 causes a major cell stress in both CD4 and CD8 thymocyte populations. Of note, PSMB11-deficiency had no impact on medullary thymic epithelial cells (mTECs), which originate from progenitors that express PSMB11 early in ontogeny. Conclusion: We conclude that PSMB11 has pervasive effects on both CD4 and CD8 thymocytes via regulation of gene expression in cTECs.
2019-01-01 | GSE107535 | GEO
Project description:Purpose: Cortical thymic epithelial cells (cTECs) contain a unique type of proteasomes, thymoproteasomes. Indirect evidence suggests that the key role of PSMB11, a catalytic subunit of thymoproteasomes specific to cTECs, is to generate a unique repertoire of MHC I peptides. Notably, PSMB11-deficient mice display defective development of CD8 thymocytes. The objective of this study was to characterize the impact of PSMB11 on cTECs and thymocyte development. Since different types of proteasomes have non-redundant effects on gene expression, we hypothesized that thymoproteasomes should have a distinct impact on the transcriptome and thereby the function of cTECs. Results: We report that PSMB11 in cortical thymic epithelial cells has dramatic effects on cTECs on both CD4 and CD8 thymocyte populations. PSMB11 modulates the expression of 850 genes in cTECs, 582 in CD4 thymocytes and 284 in CD8 thymocytes. PSMB11-regulated cTEC genes are involved mainly in cell-cell adhesion, extracellular matric organization and thymocyte chemotaxis. PSMB11-deficient cTECs acquire features of mTECs and perturb thymocyte development. Deletion of PSMB11 causes a major cell stress in both CD4 and CD8 thymocyte populations. Of note, PSMB11-deficiency had no impact on medullary thymic epithelial cells (mTECs), which originate from progenitors that express PSMB11 early in ontogeny. Conclusion: We conclude that PSMB11 has pervasive effects on both CD4 and CD8 thymocytes via regulation of gene expression in cTECs.
2019-01-01 | GSE107536 | GEO
Project description:Purpose: Cortical thymic epithelial cells (cTECs) contain a unique type of proteasomes, thymoproteasomes. Indirect evidence suggests that the key role of PSMB11, a catalytic subunit of thymoproteasomes specific to cTECs, is to generate a unique repertoire of MHC I peptides. Notably, PSMB11-deficient mice display defective development of CD8 thymocytes. The objective of this study was to characterize the impact of PSMB11 on cTECs and thymocyte development. Since different types of proteasomes have non-redundant effects on gene expression, we hypothesized that thymoproteasomes should have a distinct impact on the transcriptome and thereby the function of cTECs. Results: We report that PSMB11 has dramatic effects on cTECs and on both CD4 and CD8 thymocyte populations. PSMB11 modulates the expression of 850 genes in cTECs, 582 in CD4 thymocytes and 284 in CD8 thymocytes. PSMB11-regulated cTEC genes are involved mainly in cell-cell adhesion, extracellular matric organization and thymocyte chemotaxis. PSMB11-deficient cTECs acquire features of mTECs and perturb thymocyte development. Moreover, we found that deletion of PSMB11 causes a major cell stress in both CD4 and CD8 thymocyte populations. Of note, PSMB11-deficiency had no impact on medullary thymic epithelial cells (mTECs), which originate from progenitors that express PSMB11 early in ontogeny. Conclusion: We conclude that PSMB11 has pervasive effects on both CD4 and CD8 thymocytes via regulation of gene expression in cTECs.
2019-01-01 | GSE107534 | GEO
Project description:Thymic epithelial cells (TECs) support T cell development in the thymus. Cortical thymic epithelial cells (cTECs) facilitate positive selection of developing thymocytes whereas medullary thymic epithelial cells (mTECs) facilitate the deletion of self-reactive thymocytes in order to prevent autoimmunity. The mTEC compartment is highly dynamic with continuous maturation and turnover, but the genetic regulation of these processes remains poorly understood. MicroRNAs (miRNAs) are important regulators of TEC genetic programs since miRNA-deficient TECs are severely defective. However, the individual miRNAs important for TEC maintenance and function and their mechanisms of action remain unknown. Here, we demonstrate that miR-205 is highly and preferentially expressed in mTECs during both thymic ontogeny and in the postnatal thymus. This distinct expression is suggestive of functional importance for TEC biology. Genetic ablation of miR-205 in TECs, however, neither revealed a role for miR-205 in TEC function during homeostatic conditions nor during recovery from thymic stress conditions. Thus, despite its distinct expression, miR-205 on its own is largely dispensable for mTEC biology. In order to identify miRNAs differentially expressed in mTECs, we purified cortical thymic epithelial cells (cTECs), mTECs and CD45+ cells as three distinct populations and prepared RNA for microarray analysis. Thymic subsets were FACS-purified from 4-week old NOD wildtype mice. Thymi from 10-12 female mice were pooled together for stromal cell isolation for a total of 3 CD45+, 2 cTEC and 3 mTEC biologic replicates.
2015-07-28 | E-GEOD-68674 | biostudies-arrayexpress
Project description:Antigen presentation by cortical and medullary thymic epithelial cells (cTEC and mTEC) ensures the formation of a self-restricted and self-tolerant T cell repertoire, respectively. As such, a broad diversity of self-antigens needs to be presented by mTEC to induce T cell’s self-tolerance. Even though the expression and antigen presentation of protein coding genes in mTEC has been abundantly described, little is known of the implication of allegedly noncoding regions of the genome to tolerance induction. In this study, we focused on transposable elements (TE), which have been shown to be highly expressed by mTEC.
2024-04-17 | PXD042241 | Pride
Project description:We used Affymetrix microarrays to understand the genome wide differences in Adult and fetal cortical thymic epithelial cells (cTEC) and medullary thymic epithelial cells (mTEC)
2017-02-10 | GSE81433 | GEO
Project description:Antigen presentation by cortical and medullary thymic epithelial cells (cTEC and mTEC) ensures the formation of a self-restricted and self-tolerant T cell repertoire, respectively. As such, a broad diversity of self-antigens needs to be presented by mTEC to induce T cell\u2019s self-tolerance. Even though the expression and antigen presentation of protein coding genes in mTEC has been abundantly described, little is known of the implication of allegedly noncoding regions of the genome to tolerance induction. In this study, we focused on transposable elements (TE), which have been shown to be highly expressed by mTEC.
2024-04-16 | GSE232011 | GEO
Project description:Thymic epithelial cells (TEC) control T cell development and play essential roles in establishing self-tolerance. Transcription factors controlling TEC development are poorly characterized. We report that Klf6 plays a critical role in TEC development. Mice deficient for Klf6 in TEC had a hypoplastic thymus - evident from fetal stages into adulthood. Proliferation of TEC was not reduced, but a dramatic increase in the frequency of apoptotic TEC in fetal and adult thymus was observed. Among cortical TEC (cTEC), we found expansion of a previously unreported cTEC population expressing the transcription factor Sox10. Medullary TEC (mTEC) subsets were not equally impacted with Ccl21a+ mTEC I and Tuft-like mTEC IV being disproportionately affected. Consistent with these TEC defects, naïve conventional T cells and NKT cells were reduced in the spleen, and signs of autoimmunity were evident. Thus, Klf6 has a pro- survival role in TEC and is also required for differentiation of the mTEC I and mTEC IV populations of TEC in adult mice. In this work, we report that mice with Foxn1-Cre mediated ablation of Klf6 in TEC demonstrate thymic hypoplasia beginning from prenatal life and extending through adulthood. Guided by single-cell transcriptional profiling, we determined that loss of Klf6 increased programmed cell death of TEC in prenatal and adult mice. In adult mice, thymic Klf6 deficiency severely impacted the mTEC I and mTEC IV populations. In addition, Klf6 deficiency led to the expansion of a previously uncharacterized cTEC population expressing Sox10 that is present in wild-type mice at very low frequencies. We observed concordant reductions of the naïve αβ T cell and iNKT pools in the periphery of young adult mice. Furthermore, we detected T cell infiltration in salivary and lacrimal glands, indicating defects in T cell tolerance.
2023-10-12 | GSE221073 | GEO
Project description:Thymic epithelial cells (TEC) control T cell development and play essential roles in establishing self-tolerance. Transcription factors controlling TEC development are poorly characterized. We report that Klf6 plays a critical role in TEC development. Mice deficient for Klf6 in TEC had a hypoplastic thymus - evident from fetal stages into adulthood. Proliferation of TEC was not reduced, but a dramatic increase in the frequency of apoptotic TEC in fetal and adult thymus was observed. Among cortical TEC (cTEC), we found expansion of a previously unreported cTEC population expressing the transcription factor Sox10. Medullary TEC (mTEC) subsets were not equally impacted with Ccl21a+ mTEC I and Tuft-like mTEC IV being disproportionately affected. Consistent with these TEC defects, naïve conventional T cells and NKT cells were reduced in the spleen, and signs of autoimmunity were evident. Thus, Klf6 has a pro- survival role in TEC and is also required for differentiation of the mTEC I and mTEC IV populations of TEC in adult mice. In this work, we report that mice with Foxn1-Cre mediated ablation of Klf6 in TEC demonstrate thymic hypoplasia beginning from prenatal life and extending through adulthood. Guided by single-cell transcriptional profiling, we determined that loss of Klf6 increased programmed cell death of TEC in prenatal and adult mice. In adult mice, thymic Klf6 deficiency severely impacted the mTEC I and mTEC IV populations. In addition, Klf6 deficiency led to the expansion of a previously uncharacterized cTEC population expressing Sox10 that is present in wild-type mice at very low frequencies. We observed concordant reductions of the naïve αβ T cell and iNKT pools in the periphery of young adult mice. Furthermore, we detected T cell infiltration in salivary and lacrimal glands, indicating defects in T cell tolerance.
2023-10-12 | GSE220270 | GEO
Project description:Purpose: In all vertebrates, the thymus is necessary and sufficient for production of classic adaptive T cells. The key components of the thymus are cortical and medullary thymic epithelial cells (cTECs and mTECs). Despite the capital role of TECs, our understanding of TEC biology is quite rudimentary. For instance, we ignore what might be the extent of divergence in the functional program of these two TECs populations. It also remains unclear why the number of TECs decreases rapidly with age, thereby leading to progressive thymic insufficiency. Methods: Systems level understanding of cell function begins with gene expression profiling, and the transcriptome is currently the only '-ome' that can be reliably tackled in its entirety in freshly harvested primary cells. In order to gain novel insights into TEC biology, we therefore decided to analyse the whole transcriptome of cTECs, mTECs and skin epithelial cells. We elected to analyse gene expression using RNA-seq rather microarrays because RNA-seq has higher sensitivity and dynamic range coupled to lower technical variations. Results: Our deep sequencing approach provides a unique perspective into the transcriptome of TECs. Consistent with their ability to express ectopic genes, we found that mTECs expressed more genes than other cell populations. Out of a total of 15,069 genes expressed in TECs, 25% were differentially expressed by at least 5-fold in cTECs vs. mTECs. Genes expressed at higher levels in cTECs than mTECs regulate numerous cell functions including cell differentiation, cell movement and microtubule dynamics. Almost all positive regulators of the cell cycle were overexpressed in skin ECs relative to TECs. Conclusions: Our RNA-seq data provide novel insights into the transcriptional landscape of TECs, highlight substantial divergences in the transcriptome of TEC subsets and suggest that cell cycle progression is differentially regulated in TECS and skinECs. We believe that our work will therefore represent a valuable resource and will be of great interest to readers working in biological sciences, particularly in the areas of immunology and systems biology. The mRNA profiles of cTEC, mTEC (from 14 thymi of 7-days old C57BL/6 mice) and skinEC (from the trunk and dorsum of seven newborn mice) were generated by RNA-sequencing using Illumina HiSeq2000.
2013-05-07 | E-GEOD-44945 | biostudies-arrayexpress