Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA298877 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR2657950.fastq.gz | Fastqsanger.gz | |||
| SRR2657960_1.fastq.gz | Fastqsanger.gz | |||
| SRR2657960_2.fastq.gz | Fastqsanger.gz | |||
| SRR2657941.fastq.gz | Fastqsanger.gz | |||
| SRR2657951.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 26 |
Similar Datasets
Project description:Although blood-brain barrier (BBB) compromise is central to the etiology of diverse central nervous system (CNS) disorders, endothelial receptor proteins that control BBB function are poorly defined. The endothelial G protein-coupled receptor (GPCR) Gpr124 has been reported to be required for normal forebrain angiogenesis and BBB function in mouse embryos, but the role of this receptor in adults is unknown. Here, conditional Gpr124 knockout (CKO) in the endothelia of adult mice did not affect homeostatic BBB integrity but resulted in BBB disruption and microvascular hemorrhage in mouse models of ischemic stroke and glioblastoma, accompanied by reduced cerebrovascular canonical Wnt/beta-catenin signaling. Constitutive activation of Wnt/beta-catenin signaling fully corrected the BBB disruption and hemorrhage defects of Gpr124 cko mice, with rescue of the endothelial tight junction, pericyte coverage and extracellular-matrix deficits. We thus identify Gpr124 as an endothelial GPCR specifically required for endothelial Wnt signaling and BBB integrity under pathological conditions in adult mice. This finding implicates Gpr124 as a potential therapeutic target for human CNS disorders characterized by BBB disruption.
2017-03-06 | GSE74052 | GEO
Project description:Canonical Wnt signaling in endothelial cells (ECs) is required for vascularization of the central nervous system (CNS) and for formation and maintenance of barrier properties unique to CNS vasculature. Gpr124 is an orphan member of the adhesion G-protein-coupled receptor family that is expressed in ECs and is essential for CNS angiogenesis and barrier formation via an unknown mechanism. Using canonical Wnt signaling assays in cell culture and genetic loss- and gain-of-function experiments in mice, we show that Gpr124 functions as a co-activator of Wnt7a- and Wnt7b-stimulated canonical Wnt signaling via a Frizzled receptor and Lrp co-receptor, and that Gpr124-stimulated signaling functions in concert with Norrin/Frizzled4 signaling to control CNS vascular development. These experiments identify Gpr124 as a ligand-specific co-activator of canonical Wnt signaling. Total mRNA from HEK-293/STF cells was subjected to RNAseq
2014-08-20 | E-GEOD-60529 | biostudies-arrayexpress
Project description:The GPR124/RECK/WNT7 pathway essentially regulates central nervous system angiogenesis and blood-brain barrier (BBB) function. GPR124, a brain endothelial adhesion 7-pass transmembrane protein, associates with membrane RECK, which binds and stabilizes newly synthesized WNT7 for subsequent transfer to Frizzled (FZD) and canonical b-catenin signaling. GPR124 function remains enigmatic; while its extracellular domain (ECD) is required, the poorly conserved intracellular domain (ICD) appears to be variably required in mammals versus zebrafish, potentially mediated by bridging of the GPR124 and FZD ICDs by intracellular adaptor proteins. GPR124 ICD deletion mutants impair zebrafish angiogenesis, but paradoxically still mediate WNT7 signaling upon mammalian cell transfection. We thus further investigated the GPR124 C-terminal ICD by deletion in mice (Gpr124ΔC). Notably, Gpr124ΔC/ΔC mice could be born and did not recapitulate Gpr124-/- embryonic lethal forebrain hemorrhage. GPR124ΔC protein was inefficiently expressed, resulting in mild, hypomorphic, non-hemorrhagic defects in CNS angiogenesis and BBB function, sparing the cortex and only confined to ganglionic eminences. Impaired surface expression of GPR124ΔC directly correlated with reduced endothelial WNT signaling, arguing against an intrinsic signaling deficiency. Further, GPR124ΔC and recombinant GPR124 ECD both rescued WNT7 signaling following brain endothelial Gpr124 knockdown. Thus, in mice, the GPR124 essential regulation of WNT7-dependent CNS forebrain angiogenesis and BBB function is exerted by ICD-independent functionality, extending the range of signaling mechanisms used by adhesion 7-pass transmembrane receptors.
2024-04-19 | GSE225367 | GEO
Project description:Canonical Wnt signaling in endothelial cells (ECs) is required for vascularization of the central nervous system (CNS) and for formation and maintenance of barrier properties unique to CNS vasculature. Gpr124 is an orphan member of the adhesion G-protein-coupled receptor family that is expressed in ECs and is essential for CNS angiogenesis and barrier formation via an unknown mechanism. Using canonical Wnt signaling assays in cell culture and genetic loss- and gain-of-function experiments in mice, we show that Gpr124 functions as a co-activator of Wnt7a- and Wnt7b-stimulated canonical Wnt signaling via a Frizzled receptor and Lrp co-receptor, and that Gpr124-stimulated signaling functions in concert with Norrin/Frizzled4 signaling to control CNS vascular development. These experiments identify Gpr124 as a ligand-specific co-activator of canonical Wnt signaling.
2014-08-20 | GSE60529 | GEO
Project description:Vascular smooth muscle cells (VSMC) are important for contraction, blood flow distribution and regulation of blood vessel diameter, but to what extent they contribute to the integrity of blood vessels and blood-brain barrier function is less well understood. In this report, we explored the impact of the progressive loss of VSMC in the Notch3-/- mouse on blood vessel integrity in the central nervous system To explore the molecular consequences of the VSMC phenotype in Notch3-/- mice, we performed genome-wide transcriptional profiling of the brain vasculature in mutants and littermate controls using Affymetrix Mouse Genome 430 2.0 Array.
2015-02-18 | GSE55203 | GEO
Project description:Stroke is the second leading cause of death in human life health, but current treatment strategies are limited to thrombolytic therapy, and because of the tight time window, many contraindications, and only a very small number of people can benefit from it, new therapeutic strategies are needed to solve this problem. As a physical barrier between the central nervous system and blood, the blood-brain barrier (BBB) maintains the homeostasis of the central nervous system. Maintaining the integrity of the BBB may emerge as a new therapeutic strategy. Liquiritin (LQ) is a flavonoid isolated from the medicinal plant Glycyrrhiza uralensis, and this study aims to investigate the protective effects of LQ on brain microvascular endothelial cells (BMECs), to provide a new therapeutic strategy for stroke treatment, and also to provide research ideas for the development of traditional Chinese medicine (TCM).
2021-04-25 | PXD025605 |
Project description:Vascular smooth muscle cells (VSMC) are important for contraction, blood flow distribution and regulation of blood vessel diameter, but to what extent they contribute to the integrity of blood vessels and blood-brain barrier function is less well understood. In this report, we explored the impact of the progressive loss of VSMC in the Notch3-/- mouse on blood vessel integrity in the central nervous system To explore the molecular consequences of the VSMC phenotype in Notch3-/- mice, we performed genome-wide transcriptional profiling of the brain vasculature in mutants and littermate controls using Affymetrix Mouse Genome 430 2.0 Array. Three Notch3 knockout and three littermate control mice at age of 2 months were used to profile the transcriptomes. Total RNA was extracted from cerebral and cerebellar microvascular fragments and hyrbridized separately on the Mouse Genome 430 2.0 Array according to standard procedures.
2015-02-18 | E-GEOD-55203 | biostudies-arrayexpress
Project description:In chronic inflammatory diseases of the central nervous system (CNS), immune cells persisting behind the blood-brain barrier are supposed to promulgate local tissue destruction. The drivers of such compartmentalized inflammation remain unclear, but tissue-resident memory T cells (TRM) represent a potentially important cellular player in this process
2022-02-19 | E-MTAB-11422 | biostudies-arrayexpress
Project description:In chronic inflammatory diseases of the central nervous system (CNS), immune cells persisting behind the blood-brain barrier are supposed to promulgate local tissue destruction. The drivers of such compartmentalized inflammation remain unclear, but tissue-resident memory T cells (TRM) represent a potentially important cellular player in this process
2022-03-14 | E-MTAB-11511 | biostudies-arrayexpress
Project description:The existence of the blood-brain barrier (BBB) dramatically limits the drug treatment of central nervous system diseases such as stroke, neurodegenerative diseases, and brain tumors. Due to the complexity of the structure and function of the blood-brain barrier, it has been challenging to develop central nervous system drug delivery strategies and reveal critical biological mechanisms. Our previous studies have confirmed that specific mode electroacupuncture stimulation (EA) can effectively open the BBB in rats. Here, we utilized single-cell RNA sequencing (scRNA-seq) to map the cell population of rat cerebral cortex comprehensively. We identified 23 cell subsets and 8 types of cells in the brain obtained by cell annotation, and explored the potential mechanism of EA to open the blood-brain barrier by bioinformatics analysis of specific cell subsets and cell types, as well as cell communications. In summary, scRNA-seq uncovers the transcriptional changes of the cerebral cortex under EA at the single cell level; our results provide rich insights into the molecular and cellular architecture changes of the brain after EA intervention and provide a new reference for BBB material transport and its drug delivery research in health and disease, providing new potential strategies into the mechanism of BBB opening and provide essential information for designing rational treatment regimens and optimizing drug delivery.
2024-07-24 | GSE272895 | GEO