Qualitative changes in cortical thymic epithelial cells drive postpartum thymic regeneration.
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA576177 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10237700.fastq.gz | Fastqsanger.gz | |||
| SRR10237701.fastq.gz | Fastqsanger.gz | |||
| SRR10237702.fastq.gz | Fastqsanger.gz | |||
| SRR10237703.fastq.gz | Fastqsanger.gz | |||
| SRR10237704.fastq.gz | Fastqsanger.gz |
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Project description:During gestation, sex hormones cause a significant thymic involution which enhances fertility. This thymic involution is rapidly corrected following parturition. As thymic epithelial cells (TECs) are responsible for the regulation of thymopoiesis, we analyzed the sequential phenotypic and transcriptomic changes in TECs during the postpartum period in order to identify mechanisms triggering postpartum thymic regeneration. In particular, we performed flow cytometry analyses and deep RNA-sequencing on purified TEC subsets at several time points before and after parturition. We report that pregnancy-induced involution is not caused by loss of TECs since their number does not change during or after pregnancy. However, during pregnancy, we observed a significant depletion of all thymocyte subsets downstream of the double-negative 1 (DN1) differentiation stage. Variations in thymocyte numbers correlated with conspicuous changes in the transcriptome of cortical TECs (cTECs). The transcriptomic changes affected predominantly cTEC expression of Foxn1, its targets and several genes that are essential for thymopoiesis. By contrast, medullary TECs (mTECs) showed very little transcriptomic changes in the early postpartum regenerative phase, but seemed to respond to the expansion of single-positive (SP) thymocytes in the late phase of regeneration. Together, these results show that postpartum thymic regeneration is orchestrated by variations in expression of a well-defined subset of cTEC genes, that occur very early after parturition.
2019-11-20 | GSE138494 | GEO
Project description:During gestation, sex hormones cause a significant thymic involution which enhances fertility. This thymic involution is rapidly corrected following parturition. As thymic epithelial cells (TECs) are responsible for the regulation of thymopoiesis, we analyzed the sequential phenotypic and transcriptomic changes in TECs during the postpartum period in order to identify mechanisms triggering postpartum thymic regeneration. In particular, we performed flow cytometry analyses and deep RNA-sequencing on purified TEC subsets at several time points before and after parturition. We report that pregnancy-induced involution is not caused by loss of TECs since their number does not change during or after pregnancy. However, during pregnancy, we observed a significant depletion of all thymocyte subsets downstream of the double-negative 1 (DN1) differentiation stage. Variations in thymocyte numbers correlated with conspicuous changes in the transcriptome of cortical TECs (cTECs). The transcriptomic changes affected predominantly cTEC expression of Foxn1, its targets and several genes that are essential for thymopoiesis. By contrast, medullary TECs (mTECs) showed very little transcriptomic changes in the early postpartum regenerative phase, but seemed to respond to the expansion of single-positive (SP) thymocytes in the late phase of regeneration. Together, these results show that postpartum thymic regeneration is orchestrated by variations in expression of a well-defined subset of cTEC genes, that occur very early after parturition.
| S-EPMC6974522 | biostudies-literature
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: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.
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Project description:T cell development in the thymus is essential for cellular immunity and depends on the organotypic thymic epithelial microenvironment. Compared to other organs, the size and cellular composition of the thymus is unusually dynamic, exemplified by rapid growth and high T cell output during early stages of development, followed by a gradual loss of functional thymic epithelial cells and diminished naïve T cell production with age. Single-cell RNA sequencing (scRNA-seq) has uncovered an unexpected heterogeneity of cell types in the thymic epithelium of young and aged adult mice; however, the identities and developmental dynamics of putative pre- and postnatal epithelial progenitors have remained unresolved. Here, we combine scRNA-seq and a novel CRISPR/Cas9-based cellular barcoding system in mice to determine qualitative and quantitative changes in the thymic epithelium over time. This dual approach enabled us to identify two principal progenitor populations: an early bi-potent progenitor type biased towards cortical epithelium, and a postnatal bi-potent progenitor population biased towards medullary epithelium. We further demonstrate that continuous autocrine provision of Fgf7 leads to sustained expansion of thymic microenvironments without exhausting the epithelial progenitor pools, suggesting a strategy to modulate the extent of thymopoietic activity.
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Project description:Aire is a transcriptional regulator that induces promiscuous expression of thousands of tissue-restricted antigen (TRA) genes in medullary thymic epithelial cells (mTECs). While the target genes of Aire are well characterized, the transcriptional programs regulating its own expression remain elusive. We used Affymetrix microarrays to analyze the gene expression patterns of Aire expressing cells (mature mTECs and Thymic B cells) and compared them to control counterparts, namely immature mTECs, cortical Thymic epithelial cells and splenic B cells of tissue-restricted antigen (TRA) genes in medullary thymic epithelial cells (mTECs). While the target genes of Aire are well characterized, the transcriptional programs regulating its own expression remain elusive. We used Affymetrix microarrays to analyze the gene expression patterns of Aire expressing cells (mature mTECs and Thymic B cells) and compared them to control counterparts, namely immature mTECs, cortical Thymic epithelial cells and splenic B cells.
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Project description:Purpose: The goal of this study is to characterise expanding thymic progenitor and stem cells from whole epithelial as well as cortical, medullary thymus sub-compartments. As reference, we have sequenced skin keratinocyte progenitor and stem cells Methods: Cells have been expanded for 4 passages on mouse feeder layer cells then loaded into the 10x Genomics Chromium Platform, and sequenced using Illumina HiSeq 4000. Conclusions: Our study compared thymic progenitor and stem cells from different origin and dissected in vitro properties of thymic and skin progenitor and stem cells
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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:Thymic epithelial cells (TECs) govern thymic T lymphocyte differentiation and selection. They can be divided into cortical and medullary TECs based on their anatomical location, function and molecular features. Cortical TECs (cTECs) provide the microenvironment for the commitment of haematopoietic precursors to the T lymphoid lineage and mediate the positive selection of CD4+CD8+ double-positive thymocytes. Medullary TECs (mTECs) facilitate the negative selection of self-reactive thymocytes and the differentiation of FOXP3+ regulatory T (Treg) cells2. 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 determine the transcriptional impact of Kat7 loss, we purified mTECs and cTECs from Kat7-knockout and control mice and performed RNA-seq. The mTECs were further divided into MHCII-high and MHCII-low subsets.
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