Gene expression data from mouse brain endothelial cells after SAH
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE155137 | GEO | 2021/04/12
REPOSITORIES: GEO
Similar Datasets
Project description:The blood-brain barrier (BBB) represents a major challenge when developing central nervous system (CNS)-active therapeutics. The non-human primate (NHP)-brain endothelium constitutes an essential alternative to human in the prediction of molecule trafficking across the BBB and in the search of new brain-specific transport mechanisms. This study presents a comparison between the NHP transcriptome of freshly isolated brain microcapillaries and in vitro-selected brain endothelial cells (BECs), focusing on important BBB features – tight junctions, receptors mediating transcytosis (RMT), ABC and SLC transporters. In vitro BECs conserved most of the BBB key elements for barrier integrity and control of molecular trafficking. We also assessed the function of RMT via the Transferrin Receptor (TFRC) in the characterized NHP-BBB model, where both human transferrin and anti-hTFRC antibody showed increased apical-to-basolateral passage in comparison to control molecules. In parallel, we investigated eventual BBB-related regional differences in 7-day in vitro-selected BECs from 5 brain structures: brainstem, cerebellum, cortex, hippocampus and striatum. Our analysis retrieved very few differences in the brain endothelium from these 5 brain regions, suggesting a rather homogeneous BBB role and function across the brain parenchyma. In conclusion, the presently established NHP-derived BBB model closely mimics the physiological BBB, therefore representing a ready-to-use tool for assessment of the penetration of biotherapeutics into the human CNS.
2020-07-23 | GSE154901 | GEO
Project description:The Wnt signaling pathway regulates blood-brain barrier (BBB) formation and function in both development and pathogenesis of diseases, and is essential for CNS angiogenesis and BBB formation in both embryonic and postnatal development. However, how Wnt signaling affects brain tumor endothelial cells is largely unknown. We isolated endothelial cells from tumors in control or LGK974 treated mice, and analyzed the role of Wnt signaling inhibition on tumor endothelial cells.
2023-03-31 | GSE203374 | GEO
Project description:To understand the molecular mechanisms during the maturation of cord blood-derived endothelial cells into blood brain barrier capillary endothelial cells (BCECs), we have employed whole genome microarray expression profiling to identify genes responsible for the maturation process. Hematopoietic stem cells were isolated from cord-blood samples and differentiated into endothelial cells. The endothelial cells were further maturated into BCECs by co-culturing with blood-brain barrier (BBB) specific cells (pericytes) for 3 days and 6 days.
2013-10-18 | GSE45171 | GEO
Project description:To understand the molecular mechanisms during the maturation of cord blood-derived endothelial cells into blood brain barrier capillary endothelial cells (BCECs), we have employed whole genome microarray expression profiling to identify genes responsible for the maturation process. Hematopoietic stem cells were isolated from cord-blood samples and differentiated into endothelial cells. The endothelial cells were further maturated into BCECs by co-culturing with blood-brain barrier (BBB) specific cells (pericytes) for 3 days and 6 days. The gene expression in human hematopoietic stem cell-derived endothelial cells was measured at 3 and 6 days after co-culture with pericytes. Three independent experiments were performed at each time (3 or 6 days). The RNA obtained from different experiments were pooled together for each group before microarray studies.
2013-10-18 | E-GEOD-45171 | biostudies-arrayexpress
Project description:The blood-brain barrier (BBB) consists of specific physical barriers, enzymes and transporters, which together maintain the necessary extracellular environment of the central nervous system (CNS). The main physical barrier is found in the CNS endothelial cell, and depends on continuous complexes of tight junctions combined with reduced vesicular transport. Other possible constituents of the BBB include extracellular matrix, astrocytes and pericytes, but the relative contribution of these different components to the BBB remains largely unknown. Here we demonstrate a direct role of pericytes at the BBB in vivo. Using a set of adult viable pericyte-deficient mouse mutants we show that pericyte deficiency increases the permeability of the BBB to water and a range of low-molecular-mass and high-molecular-mass tracers. The increased permeability occurs by endothelial transcytosis, a process that is rapidly arrested by the drug imatinib. Furthermore, we show that pericytes function at the BBB in at least two ways: by regulating BBB-specific gene expression patterns in endothelial cells, and by inducing polarization of astrocyte end-feet surrounding CNS blood vessels. Our results indicate a novel and critical role for pericytes in the integration of endothelial and astrocyte functions at the neurovascular unit, and in the regulation of the BBB. The brain microvascular fragments were isolated from mice with different genotypes, each represented by 3-4 biological replicates. Genotypes 1-2: Platelet derived growth factor-B (PDGF-B) retention-motif knockout (pdgfbret/ret) represent the pericyte-deficient situation, and the heterozygous mice (pdgfbret/+) are used as controls. Genotypes 3-4: Hypomorphic PDGF-B mutants that rescue pdgfb-/- null mice, in which a one copy of a conditionally silent human PDGF-B transgene targeted to the Rosa 26 locus (R26P) is turned on by endothelial-specific expression of Cre recombinase. In this data set these mice are named as Tie2Cre, R26P+/0, pdgfb-/- (representing the pericyte-deficient situation). Mice wt for pdgfb (pdgfb+/+) and carrying one silent copy of R26P (R26P+/0), are used as controls. Genotype 5: Adult Notch3+/+ wildtype (WT).
2010-10-21 | E-GEOD-15892 | biostudies-arrayexpress
Project description:The precise regulation of blood-brain-barrier (BBB) permeability for immune cells and blood-borne substances is essential to maintain brain homeostasis. Sphingosine-1-phosphate (S1P), a lipid signaling molecule enriched in plasma, is known to affect BBB permeability. Previous studies focussed on endothelial S1P receptors 1 and 2, reporting a barrier-protective effect of S1P1 and a barrier-disruptive effect of S1P2. Here we present novel data characterizing the expression, localization and function of the hitherto exclusively immunce cell-associated S1P receptor 4 (S1P4) on primary brain microvascular endothelial cells (BMECs). We detected a robust expression of S1P4 in homeostatic BMECs and pinpointed its localization to abluminal endothelial membranes by electron microscopy. Basolateral S1P treatment of BMECs led to increased permeability in vitro associated with S1P4 downregulation. Likewise, downregulation of S1P4 was observed in mouse brain microvessels after stroke, a neurological disease associated with BBB impairment. RNA sequencing analysis of BMECs suggested involvement of S1P4 in endothelial homeostasis, apicobasal polarity and barrier function. Using siRNA, pharmacological agonists and antagonists of S1P4 both in vitro and in vivo, we demonstrate a barrier-protective function of S1P4. We therefore suggest S1P4 as a novel target regulating BBB permeability and propose its therapeutic targeting in CNS diseases associated with BBB dysfunction.
2021-10-04 | GSE163561 | GEO
Project description:The brain and spinal cord are endowed with particular vascular systems, known as the blood-brain barrier (BBB) and blood-spinal cord barrier (BSCB) respectively, which maintain homeostasis between nervous parenchyma and peripheral circulation. Despite these common features, the BSCB presents structural and functional differences resulting in distinct vulnerability to pathological insults when compared to the BBB. Although, the heterogeneity of endothelial cell types underlies their remarkable ability to sub-specialize and provide specific requirements for a given vascular bed, very little is known concerning intrinsic differences between microvascular endothelial cells (MECs) derived from brain (BMECs) and spinal cord (SCMECs), including their response to inflammation. We used Agilent Whole Rattus Genome Microarray 4X44K to compare rat BMECs and SCMECs in both basal and inflammatory conditions; TNF-α-induced, TWEAK-induced and LPS-induced gene expression after 6 hr, 12 hr, 24 hr and 48 hr incubation.
2016-06-20 | E-MTAB-4696 | biostudies-arrayexpress
Project description:Functional and structural dysfunction of the blood brain barrier (BBB) leads to severe alterations in brain physiology and is believed to trigger neurodegeneration. To investigate the molecular mechanisms driving the BBB dysfunction, very few human BBB cell culture models are available; of which, the human microvascular endothelial cell line (hCMEC/D3) is the most widely used. Thus far, array-based approaches or targeted seqeuncing based approaches have been employed to characterize the gene expression of the hCMEC/D3 model. However,The goal of this study is to perform deep transcriptomic sequencing of the BBB cell line and obtain features like gene expression, expressed single nucleotide variants, alternate splice forms, circular RNAs, long non-coding RNAs and micro RNAs. We have developed blood brain barriers transcriptomics landscape using RNA sequencing and micro RNA seqeuncing data obtained from replicates of hCMEC/D3 BBB cell line.
2016-03-17 | E-GEOD-76528 | biostudies-arrayexpress
Project description:Functional and structural dysfunction of the blood brain barrier (BBB) leads to severe alterations in brain physiology and is believed to trigger neurodegeneration. To investigate the molecular mechanisms driving the BBB dysfunction, very few human BBB cell culture models are available;of which, the human microvascular endothelial cell line (hCMEC/D3) is the most widely used. Thus far, array-based approaches or targeted seqeuncing based approaches have been employed to characterize the gene expression of the hCMEC/D3 model. However,The goal of this study is to perform deep transcriptomic sequencing of the BBB cell line and obtain features like gene expression, expressed single nucleotide variants, alternate splice forms, circular RNAs, long non-coding RNAs and micro RNAs. We have developed blood brain barriers transcriptomics landscape using RNA and micro RNA sequencing data obtained from replicates of hCMEC/D3 BBB cell line.
2016-03-17 | E-GEOD-76530 | biostudies-arrayexpress
Project description:The blood-brain barrier (BBB) is a unique set of properties of the brain vasculature which severely restricts its permeability to proteins and small molecules. Classic chick-quail chimera studies showed that these properties are not intrinsic to the brain vasculature but rather are induced by surrounding neural tissue. Here we identify Spock1 as a candidate neuronal signal for regulating BBB permeability in zebrafish and mice. Mosaic genetic analysis shows that neuronally-expressed Spock1 is cell non-autonomously required for a functional BBB. Leakage in spock1 mutants is associated with altered extracellular matrix (ECM), increased endothelial transcytosis, and altered pericyte-endothelial interactions. Furthermore, a single dose of recombinant SPOCK1 into spock1 mutants quenches gelatinase activity, restores vascular expression of BBB genes including mcamb, and partially restores barrier function. These analyses support a model in which neuronally secreted Spock1 induces BBB properties by altering the ECM, thereby regulating pericyte-endothelial interactions and downstream vascular gene expression.
2023-05-01 | GSE230236 | GEO