Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA324805 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR3647300_1.fastq.gz | Fastqsanger.gz | |||
| SRR3647300_2.fastq.gz | Fastqsanger.gz | |||
| SRR3647301_1.fastq.gz | Fastqsanger.gz | |||
| SRR3647301_2.fastq.gz | Fastqsanger.gz | |||
| SRR3647302_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 24 |
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Project description:Continuous thymic homing of hematopoietic progenitor cells (HPCs) via the blood is critical for normal T cell development. However, the nature and the differentiation program of the specialized thymic endothelial cells (ECs) controlling this process remain poorly understood. Here, using conditional gene-deficient mice, we find that lymphotoxin beta receptor (LTβR) directly controls thymic ECs to guide HPC homing. Interestingly, T cell deficiency or conditional ablation of T-cell-engaged LTβR signaling results in a defect in thymic HPC homing, suggesting the feedback regulation of thymic progenitor homing by thymic products. Furthermore, we identify and characterize a special thymic portal EC population with features that guide HPC homing. LTβR is essential for the differentiation and homeostasis of these thymic portal ECs. Finally, we show that LTβR is required for T cell regeneration upon irradiation-induced thymic injury. Together, these results uncover a cellular and molecular pathway that governs thymic EC differentiation for HPC homing.
2017-02-09 | GSE83114 | GEO
Project description:Hematopoietic differentiation from human pluripotent stem cell in vitro is an important approach for the research of hematopoietic stem cell regeneration. Small molecules that can maintenance low ROS level and inhibit cell apoptosis or autophagy are benifit for the maintenance or expansion of hematopoietic stem cells. Lipoic acid (ALA) as a small antioxidant molecule can regulate the ROS level and apoptosis of cells. This study found that lipoic acid promoted the production of hemogenic endothelial cells and hematopoietic progenitor cells. Transcriptome analysis of hemogenic endothelial cells showed that ALA upregulated the endothelial to hematopoietic transition (EHT) related genes and downregulated the EHT negative regulated genes. ALA also up-regulated ROS and apoptosis related genes to inhibit the apoptosis of hematopoietic stem/progenitor cells.These results indicated that ALA might have an important role in the regeneration of hematopoietic stem progenitor cell in vitro.
2020-07-14 | GSE144307 | GEO
Project description:Age-related thymic involution, leading to reduced T cell production, is one of the major causes of immunosenescence. This results in an increased susceptibility to cancers, infections, and autoimmunity and in reduced vaccine efficacy. Here, we identified that the receptor activator of nuclear factor κB (RANK)-RANK ligand (RANKL) axis in the thymus is altered during aging. Using a conditional transgenic mouse model, we demonstrated that endothelial cells depend on RANK signaling for their cellularity and functional maturation. Decreased RANKL availability during aging resulted in a decline in cellularity and function of both endothelial cells and thymic epithelial cells, contributing to thymic involution. We then found that, whereas RANKL neutralization in young mice mimicked thymic involution, exogenous RANKL treatment in aged mice restored thymic architecture as well as endothelial cell and epithelial cell abundance and functional properties. Consequently, RANKL improved T cell progenitor homing to the thymus and boosted T cell production. This cascade of events resulted in peripheral T cell renewal and effective antitumor and vaccine responses in aged mice. Furthermore, we conducted a proof-of-concept study that showed that RANKL stimulates endothelial cells and epithelial cells in human thymic organocultures. Overall, our findings suggest that targeting the RANK-RANKL axis through exogenous RANKL administration could represent a therapeutic strategy to rejuvenate thymic function and improve T cell immunity during aging.
2024-09-30 | GSE241880 | GEO
Project description:T cell derived LTR signal regulates thymic egress via distinct thymic portal endothelial cells
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Project description:The liver exhibits a unique capacity for regeneration in response to injury. Lymphotoxin β Receptor (LTβR), a core member of the Tumor Necrosis Factor (TNF)/TNF Receptor (TNFR) superfamily is known to play an important role in this process. However, LTβR functions in the pathophysiological alterations and molecular mechanisms of liver regeneration are so far ill-characterized. Interestingly, LTβR / mice suffered from increased and prolonged liver tissue damage after 70 % hepatectomy (PHx), a finding accompanied by elevated alkaline phosphatase levels and deregulated bile acid (BA) homeostasis. Pronounced differences in the expression patterns of genes relevant for BA synthesis and recirculation were observed. Transcriptome analysis revealed a marked disparity in gene expression programs in LTβR / vs. WT liver tissue, where gene ontology (GO) terms related to transcription, gene expression and metabolic pathways were over-represented in the latter. In addition, murinoglobulin 2 (Mug2), a gene product to date not implicated in liver regeneration, was identified as one of the most differentially regulated genes after PHx in WT compared to LTβR / and TNFRp55-/- livers. LTβR and TNFRp55 share downstream signaling elements. TNFRp55 is known to also play an important role in liver regeneration after PHx. Therefore, LTβR / mice were treated with Etanercept to create mice functionally deficient in both signaling pathways. Strikingly, the combined blockade of TNFR and LTβR signaling leads to complete failure of liver regeneration resulting in death within 24 to 48 hours after PHx. LTβR is essential for efficient liver regeneration and cooperates with TNFRp55 in this process. Differences in survival kinetics strongly suggest distinct functions for these two cytokine receptors in liver regeneration. Failure of TNFR and LTβR signaling renders liver regeneration impossible.
2024-02-25 | GSE74531 | GEO
Project description:The liver exhibits a unique capacity for regeneration in response to injury. Lymphotoxin β Receptor (LTβR), a core member of the Tumor Necrosis Factor (TNF)/TNF Receptor (TNFR) superfamily is known to play an important role in this process. However, LTβR functions in the pathophysiological alterations and molecular mechanisms of liver regeneration are so far ill-characterized. Interestingly, LTβR / mice suffered from increased and prolonged liver tissue damage after 70 % hepatectomy (PHx), a finding accompanied by elevated alkaline phosphatase levels and deregulated bile acid (BA) homeostasis. Pronounced differences in the expression patterns of genes relevant for BA synthesis and recirculation were observed. Transcriptome analysis revealed a marked disparity in gene expression programs in LTβR / vs. WT liver tissue, where gene ontology (GO) terms related to transcription, gene expression and metabolic pathways were over-represented in the latter. In addition, murinoglobulin 2 (Mug2), a gene product to date not implicated in liver regeneration, was identified as one of the most differentially regulated genes after PHx in WT compared to LTβR / and TNFRp55-/- livers. LTβR and TNFRp55 share downstream signaling elements. TNFRp55 is known to also play an important role in liver regeneration after PHx. Therefore, LTβR / mice were treated with Etanercept to create mice functionally deficient in both signaling pathways. Strikingly, the combined blockade of TNFR and LTβR signaling leads to complete failure of liver regeneration resulting in death within 24 to 48 hours after PHx. LTβR is essential for efficient liver regeneration and cooperates with TNFRp55 in this process. Differences in survival kinetics strongly suggest distinct functions for these two cytokine receptors in liver regeneration. Failure of TNFR and LTβR signaling renders liver regeneration impossible.
2024-02-25 | GSE67263 | GEO
Project description:We performed RNA sequencing analyses of adult mouse bone marrow endothelial cells. Especially, we investigated gene expression profiling of endothelial cells before and after lethal irradiation or hematopoietic cell depletion. We also analyzed mouse bone marrow endothelial cell subtypes, Apln+ and diaphyseal endothelial cells. Whole bone marrow cells, lineage negative hematopoietic stem and progenitor cells, Lin- Sca1+ cKit+ cells were used as controls for the differential gene expression analyses.
2019-11-14 | GSE115422 | GEO
Project description:The ligand for the c-Kit receptor, KitL, exists as a membrane-associated (mKitL) and a soluble form (sKitL). KitL functions outside c-Kit activation have not been identified. We show that co-culture of c-Kit– and mKitL–expressing NIH3T3 cells results in signaling through mKitL: c-Kit–bound mKitL recruits calcium-modulating cyclophilin ligand (CAML) to selectively activate Akt, leading to CREB phosphorylation, mTOR pathway activation, and increased cell proliferation. Activation of mKitL in thymic vascular endothelial cells (VECs) induces mKitL- and Akt-dependent proliferation, and genetic ablation of mKitL in thymic VECs blocks their c-Kit responsiveness and proliferation during neonatal thymic expansion. Therefore, mKitL–c-Kit form a bi-directional signaling complex that acts in the developing thymus to coordinate thymic VEC and early thymic progenitor (ETP) expansion by simultaneously promoting ETP survival and VEC proliferation. This mechanism may be relevant to both normal tissues and malignant tumors that depend on KitL–c-Kit signaling for their proliferation.
2018-11-21 | PXD011061 | Pride
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
Project description:Preservation of cell identity is necessary for homeostasis of most adult tissues. This process is challenged every time a tissue undergoes regeneration after stress or injury. In the lethal Duchenne muscular Dystrophy (DMD), skeletal muscle regenerative capacity declines gradually as fibrosis increases. Using genetically engineered-tracing mice, we demonstrate that in dystrophic muscle, specialized cells of muscular, endothelial and hematopoietic origins gain plasticity towards a fibrogenic fate via a TGFβ-mediated pathway. This results in loss of cellular identity and normal function, with deleterious consequences for regeneration. Furthermore, this fibrogenic process involves acquisition of a mesenchymal progenitor multipotent status, illustrating a link between fibrogenesis and gain of progenitor cell functions. As this plasticity was also observed in DMD patients, we propose that mesenchymal transitions impair regeneration and worsen diseases with a fibrotic component. TGFb exposure induced gene expression was measured after 4 days of treatment compared to untreated cells. Three independent experiments were performed both for the treatment and for the control
2015-04-09 | E-GEOD-67687 | biostudies-arrayexpress