Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE138494 | GEO | 2019/11/20

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Next-generation sequencing of cTEC and mTEC isolated from non-pregnant and pregnant females lacking the expression of Klf4 (KO) or not (LOX)

Project description:Stress-induced thymic involution is defined by profound damage to thymic epithelial cells (TECs), resulting in an acute and transient reduction of thymopoietic capacity. During pregnancy, thymic involution is not associated with TEC loss but rather with TEC quality modifications. Study of the mechanisms of TEC maintenance during pregnancy may be of critical importance for identifying new players for thymic regeneration in other models of thymic involution. We report a strong enrichment for motifs recognized by KLF4 based on genes differentially expressed in TECs of pregnant females. Therefore, we studied the impact of Klf4 deletion in TECs during pregnancy by analyzing thymus composition and TEC transcriptome. Conditional Klf4 deletion in homeostatic conditions does not injure thymic integrity. However, pregnant females lacking Klf4 show a disrupted thymus with substantial loss of thymic epithelial cells. Klf4 maintains cTEC number during pregnancy by maintaining cell survival and inhibiting the transition to a mesenchymal state. Our study reveals Klf4 as a protective factor for TECs during pregnancy-associated thymic involution and represents a potential study subject for other models of stress-induced thymic involution.

2022-09-30 | GSE210885 | GEO

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. 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.

2014-09-12 | E-GEOD-56928 | biostudies-arrayexpress

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.

2019-06-06 | GSE132278 | GEO

Zuklys etal_miRNA_C57BL6_TECs

Project description:Thymic epithelial cells (TECs) were isolated from 2 week old C57BL/6 mice by cell sorting of supbopulations: cTEC (CD45-,EpCAM+, MHCII+, UEA-1-, Ly51+) and mTEC(CD45-,EpCAM+, MHCII+, UEA-1-, Ly51+). Total RNA (80-100ng) extracted from sorted cells was subjected to labeling and hybridisation.

2022-12-29 | E-MEXP-3308 | biostudies-arrayexpress

The cortical thymic epithelial cell compartment is shaped by stage-specific thymocyte crosstalk which drives loss of Foxn1 and its key target genes

Project description:In the thymus, cortical and medullary thymic epithelial cells (TEC) support the production of abT-cells from bone marrow-derived progenitors. For cortical TEC (cTEC), the expression a specialised gene signature that encodes multiple key regulators including CXCL12, Delta-like 4 (DLL4) and b5t enables the cortex to support T-lineage commitment, and the generation and selection of CD4+CD8+ thymocytes. While the importance of the cTEC in T-cell development are well defined, the mechanisms that shape the cTEC compartment and maintain its functional specialisation are unclear. Using CXCL12DsRed reporter mice, we show that changes in expression of the chemokine CXCL12 reveal a developmentally regulated programme of cTEC heterogeneity. While cTEC uniformly express CXCL12 during neonatal stages, progression through postnatal life triggers the appearance of CXCL12- cTEC subset that continues to reside in the cortex. We show the appearance of CXCL12- cTEC is influenced by the maturation of CD4-CD8-, but not CD4+CD8+ thymocytes, demonstrating stage-specific thymocyte crosstalk controls cTEC heterogeneity. Importantly, while fate mapping experiments show that both CXCL12+ and cTEC12- cTEC arise from cells expressing Foxn1, RNA sequencing analysis shows they are genetically distinct. Thus, CXCL12- cTEC lack Foxn1 expression, which directs loss of the Foxn1-dependent cTEC gene signature that may explain the reduced capacity of CXCL12- cTEC for thymocyte interactions. In sum, our study shows that shaping of cTEC compartment during the life-course occurs via stage-specific thymocyte crosstalk which drives loss of Foxn1 and its key target genes, that may then determine the functional competence of the thymic cortex.

2022-10-28 | GSE205940 | GEO

Temporal changes of gene expression in bovine endometrium after parturition

Project description:To clarify the regenerative mechanism of endometrium after parturition in cows, mRNA expression profiles in bovine endometrium were investigated during postpartum period. after PVP-I treatment in cows. The differentially expressed genes in the endometrium between postpartum days 49-52 and days 99-101 were 23 genes, and they were much lower than those before postpartum days 49-52. This result suggests that endometrial regeneration after parturition is completely accomplished until postpartum days 49-52.

2021-01-16 | GSE164924 | GEO

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

2014-09-12 | GSE56928 | GEO

microRNA expression in thymic epithelial cells

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

AhR activation by TCDD in the ET, cortical epithelial cell line

Project description:Over activation of the aryl hydrocarbon receptor (AhR) by TCDD results ampng other phenotypes in severe thymic atrophy accompanied by immunosuppression. The link between thymic atrophy, skewed thymocyte differntiation and immunosuppression is still not fully resolved. This study investigates the TCDD elicted exprssion changes in the ET, cortical thymus epithelial cell line. Keywords: TCDD, AhR, thymic epithelial cells, thymic involution, thymus atrophy

2008-12-31 | GSE10168 | GEO

Comparison of thymic epithelial cells and hair follicle stem cells

Project description:Thymic epithelial cells (TECs) are essential for thymopoiesis and form a complex three-dimensional network, the organization of which is strikingly different from other epithelia. Interestingly, TECs express simple epithelia keratins in the cortex, stratified epithelia keratins in the medulla and epidermal differentiation markers in Hassall's bodies. Here we investigate the relationship between thymic epithelium and epidermal differentiation and show that the thymus of the rat contains a population of clonogenic TECs that can be extensively cultured and cloned using conditions developed for epidermal cell therapy in human. Clonogenic TECs conserve a thymic identity and the capacity to integrate in a thymic epithelial network, but they acquire new functionalities when exposed to an inductive skin microenvironment, permanently adopting the fate of hair follicle multipotent stem cells. This change in fate, maintained over time in serial transplantation, correlates with a down-regulation of transcription factors important for thymic identity, and an up-regulation of epidermal markers. Consequently, the TECs’ capacity to integrate in a thymic epithelial network is altered or even lost. Our results demonstrate that the thymus contains a population of holoclone-like epithelial cells that can function as bona fide multipotent keratinocyte stem cells, and that microenvironmental cues are sufficient to re-direct epithelial-cell fate, allowing crossing of primitive germ layer boundaries from endoderm to ectoderm. Keywords: Cell type comparison

2010-08-23 | GSE21686 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data