The angiopoietin-Tie2 pathway regulates Purkinje cell dendritic morphogenesis in a cell-autonomous manner
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ABSTRACT:
PROVIDER: PRJNA739970 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR14879049.fastq.gz | Fastqsanger.gz | |||
| SRR14879050.fastq.gz | Fastqsanger.gz | |||
| SRR14879051.fastq.gz | Fastqsanger.gz | |||
| SRR14879052.fastq.gz | Fastqsanger.gz | |||
| SRR14879053.fastq.gz | Fastqsanger.gz |
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Project description:Neuro-vascular communication is essential to synchronize central nervous system development. Yet, the specific cellular players, defined developmental processes and molecular mechanisms involved in this crosstalk remain poorly characterized. Here we identify the angiopoietin/Tie2 signaling axis as a crucial regulator of dendritic morphogenesis of Purkinje cells (PC) during cerebellum development. We show that in the developing cerebellum Tie2 expression is not restricted to blood vessels but it is also in PCs. Its ligands angiopoietin-1 (Ang1) and angiopoietin-2 (Ang2) are expressed in neural cells and endothelial cells (ECs), respectively. PC-specific deletion of Tie2 results in reduced dendritic arborization, which is recapitulated in neural-specific Ang1-knockout and Ang2 full-knockout mice. Mechanistically, RNA sequencing reveals that Tie2 deficient PCs present alterations in gene expression of multiple genes involved in cytoskeleton organization, dendritic formation, growth and branching. Functionally, those morphological changes are accompanied by alterations in PC network electrophysiology. Altogether, our data propose that the Ang/Tie2 signaling axis serve as mediator of intercellular communication between neural cells, ECs and PCs, required to regulate PC dendritic morphogenesis and function.
2021-12-31 | GSE178659 | GEO
Project description:Neuro-vascular communication is essential to synchronize central nervous system development. Here, we identify angiopoietin/Tie2 as a neuro-vascular signaling axis involved in regulating dendritic morphogenesis of Purkinje cells (PCs). We show that in the developing cerebellum Tie2 expression is not restricted to blood vessels, but it is also present in PCs. Its ligands angiopoietin-1 (Ang1) and angiopoietin-2 (Ang2) are expressed in neural cells and endothelial cells (ECs), respectively. PC-specific deletion of Tie2 results in reduced dendritic arborization, which is recapitulated in neural-specific Ang1-knockout and Ang2 full-knockout mice. Mechanistically, RNA sequencing reveals that Tie2-deficient PCs present alterations in gene expression of multiple genes involved in cytoskeleton organization, dendritic formation, growth, and branching. Functionally, mice with deletion of Tie2 in PCs present alterations in PC network functionality. Altogether, our data propose Ang/Tie2 signaling as a mediator of intercellular communication between neural cells, ECs, and PCs, required for proper PC dendritic morphogenesis and function.
| S-EPMC9110807 | biostudies-literature
Project description:Angiopoietin-Tie2 sytem has been inplicated in both vascular quiescence and angiogenesis. It is unclear how these two opposing signals are regulated from the same receptor-mediated intracellular signal transduction. We have noticed that Tie2 localization upon Angiopoietin stimulation depends upon the presence or absence of cell-cell contacts. Therefore, to identify the downstream signaling of Tie2 upon Angiopoietin stimulation, we performed DNA microarray analyais using RNAs obtained from confluent human umbirical vein endothelial cells (HUVECs) or sparse HUVECs stimulated with after Angiopoietin-1. There is striking difference on gene expression profile between confluent and sparse HUVECs. Keywords: endothelial cell, angiopoietin
2008-04-01 | GSE9677 | GEO
Project description:Angiopoietin-Tie2 sytem has been inplicated in both vascular quiescence and angiogenesis. It is unclear how these two opposing signals are regulated from the same receptor-mediated intracellular signal transduction. We have noticed that Tie2 localization upon Angiopoietin stimulation depends upon the presence or absence of cell-cell contacts. Therefore, to identify the downstream signaling of Tie2 upon Angiopoietin stimulation, we performed DNA microarray analyais using RNAs obtained from confluent human umbirical vein endothelial cells (HUVECs) or sparse HUVECs stimulated with after Angiopoietin-1. There is striking difference on gene expression profile between confluent and sparse HUVECs. Experiment Overall Design: To identify the genes in HUVECs which are upregulated or downregulated by the stimulation with Angiopoietin-1 in the presence (confluent) or absence (sparse) of cell-cell contacts, mRNAs were prepared from either confluent HUVECs or sparse HUVECs stimulated or unstimulated with 100 ng/ml COMP-Ang1 (more potent Angiopoietin-1). RNAs were obtained from HUVECs three times cultured independently three times and mixed as one RNA sample for further DNA microarray analyses. Experiment Overall Design: Microarray (Human Genome U133 Plus 2.0 array, Affymetrix) analyses have been performed in duplicate. Biotin labeled probes were used for the series of analyses. Hybridization and Scan were performed according to the recommendation by Affymetric. Data have been processed following the MAS 5.0 with target intensity = 100.
2008-06-16 | E-GEOD-9677 | biostudies-arrayexpress
Project description:To analyze the Angiopoietin receptor Tie2 on the arterial endothelial cells during atheroclerosis
2023-01-23 | GSE161979 | GEO
Project description:Angiopoietin-Tie2 signaling protects the kidney from ischemia-reperfusion injury in mice
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Project description:Targeting the intersection of angiopoietin-TIE2 signaling with arachidonic acid metabolism can prevent septic death
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Project description:Impaired development and maintenance of Schlemm's canal (SC) are associated with perturbed aqueous humor outflow and intraocular pressure. The angiopoietin (ANGPT)/TIE2 signaling pathway regulates SC development and maintenance, whereas the molecular mechanisms of crosstalk between SC and the neural crest (NC)-derived neighboring tissue, the trabecular meshwork (TM), are poorly understood. Here, we show NC-specific forkhead box (Fox)c2 deletion in mice results in impaired SC morphogenesis, loss of SC identity, and elevated intraocular pressure. Visible-light optical coherence tomography analysis further demonstrated functional impairment of the SC in response to changes in intraocular pressure in NC-Foxc2 -/- mice, suggesting altered TM biomechanics. Single-cell RNA-sequencing analysis identified that this phenotype is predominately characterized by transcriptional changes associated with extracellular matrix organization and stiffness in TM cell clusters, including increased matrix metalloproteinase expression, which can cleave the TIE2 ectodomain to produce soluble TIE2. Moreover, endothelial-specific Foxc2 deletion impaired SC morphogenesis because of reduced TIE2 expression, which was rescued by deleting the TIE2 phosphatase VE-PTP. Thus, Foxc2 is critical in maintaining SC identity and morphogenesis via TM-SC crosstalk.
2023-08-29 | GSE190462 | GEO
Project description:Affymetrix array gene expression analysis using RNA isolated from Purkinje cells and ventricular myocytes from the Cntn2-EGFP/ a-MHC-Cre/ floxed-tdTomato compound transgenic dual fluorescence reporter mouse Cardiac Purkinje cells are important triggers of ventricular arrhythmias associated with heritable and acquired syndromes. The mechanisms responsible for this pro-arrhythmic behavior are incompletely understood. Here, through transcriptional profiling of genetically labeled cardiomyocytes, we identified expression of Purkinje cell protein-4 (Pcp4), a putative regulator of calmodulin and Ca2+/calmodulin-dependent kinase II (CaMKII) signaling, exclusively within the His-Purkinje network. Using Pcp4-null mice and acquired cardiomyopathy models, we demonstrate that reduced expression of PCP4 is associated with CaMKII activation, abnormal electrophysiology, dysregulated intracellular calcium handling and pro-arrhythmic behavior in isolated Purkinje cells. We also show that Pcp4-null mice display profound autonomic dysregulation and arrhythmic behavior in vivo. Together, these results demonstrate that PCP4 regulates cardiac excitability through both Purkinje cell autonomous and central mechanisms and identify this modulator of CaMKII signaling as a potential arrhythmia-susceptibility candidate.
2014-11-30 | GSE60987 | GEO
Project description:Neonatal sepsis is a major cause of childhood mortality. Limited diagnostic tools and mechanistic insights have hampered our abilities to develop prophylactic or therapeutic interventions. Biomarkers in human neonatal sepsis have been repeatedly identified as associated with dysregulation of angiopoietin signaling and altered arachidonic acid metabolism. We here show that these two pathways appear to be functionally connected via reactive oxygen species (ROS) with a direct role of nitric oxide (NO). Targeting this intersection with oral administration of arachidonic acid and/or the NO donor L-arginine provided prophylactic as well as therapeutic protection from septic death.
2024-05-29 | GSE239431 | GEO