RNA expression profile of adult male and female blood brain barrier (BBB) cells of Drosophila melangaster
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PROVIDER: PRJNA660177 | ENA |
REPOSITORIES: ENA
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Project description:The RNA profile of BBB cells of adult male and female Drosophila was determined to examine the molecular basis of BBB contribution to sex-specific behavior
2020-10-31 | GSE157122 | GEO
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 an evolutionary conserved tissue interface that possesses potent chemical protection properties functioning to strictly modulate the central nervous system (CNS) microenvironment. These same properties, including tight cellular junctions and efflux transporters, also limit access of CNS-active pharmaceuticals. For this reason, understanding the molecular mechanisms that regulate BBB chemical protection is of great biomedical interest. The BBB of Drosophila consists of two surface glia layers that completely surround the brain. This tissue interface contains both “tight” cellular junctions (termed septate junctions) and drug efflux transporters; thus, the Drosophila BBB can potentially serve as a model for understanding complex regulation of BBB physiology. In this study, we show reciprocal compensatory responses following disruption of critical BBB genes: deletion of the septate junction regulator Moody causes increased drug efflux and up-regulation of the P-glycoprotein ortholog Mdr65; conversely, disruption of Mdr65 expression causes increased septate junction tightness and up-regulation of Moody. We reveal these homeostatic interactions with physiologic observations, gene expression data, and anatomical images of the BBB surface. Whole brain microarray data point to responses that are consistent with our physiologic observations and these responses are likely localized to the BBB. To our knowledge, this is the first observation of a reciprocal compensatory interaction at a tissue barrier. Furthermore, this study paves the way for future studies elucidating the direct pathways that link GPCR signaling and drug transporter regulation at the BBB. The main comparisons are between WT_new, C17 (Moody null), and PMdr65 (Mdr65 null). Since WT_new were processed on a different day than C17 and PMdr65, we also included another WT sample (WT_old) to control for genes that change depending on batch effects. Since the mutants are also in a different genetic background than WT, we also included a control that is in a similar background (UAS_control).
2013-12-31 | E-GEOD-46550 | biostudies-arrayexpress
Project description:Bacterial meningitis is a deadly disease most commonly caused by Streptococcus pneumoniae that leads to severe neurological sequelae including cerebral edema, seizures, stroke, and mortality when untreated. Meningitis is initiated by the transfer of S. pneumoniae from hematogenous source into the brain across the blood-brain barrier (BBB); the mechanisms however are still poorly understood. Current treatment strategies include adjuvant dexamethasone therapy for cerebral edema, the prime reason for neurological complications and mortality, which is followed up by antibiotics. The success of corticosteroids is however inconclusive, necessitating the development of new therapies for controlling cerebral edema. We have previously shown a general activation of hypoxia inducible factor (HIF-1α) in bacterial infections, we therefore hypothesized that HIF-1α, via induction of vascular endothelial growth factor (VEGF) is critically involved in the transmigration of pathogens across the BBB. In human and murine meningitis brain samples, HIF-1 activation was observed by immunohistochemistry. HIF-1α/VEGF expression and permeability was therefore analyzed in vitro in infected brain endothelial cells (ECs). Localization of S. pneumoniae in brain ECs from mouse/human sources was visualized in vitro and in vivo by confocal, super-resolution, and electron microscopy. S. pneumoniae infection in brain ECs resulted in upregulation of HIF-1α/VEGF by Western blotting and qRT-PCR that was associated with increased paracellular permeability, which was supported by bacterial localization at cell-cell junctions. RNA sequencing of brain microvessels from hematogenously infected mice with increased permeability and S. pneumoniae deposition in the brain showed upregulation of genes in HIF-1α/VEGF pathway. Inhibition of HIF-1α with echinomycin, siRNA in bEnd5 cells and by using primary brain ECs from HIF-1α KO mice revealed a reduced endothelial permeability and transmigration of S. pneumoniae. We thus demonstrate a critical role for HIF-1α/VEGF in transmigration of S. pneumoniae across the BBB and propose targeting this pathway to prevent BBB dysfunction in infections.
2022-09-13 | GSE122952 | GEO
Project description:Blood–brain barrier (BBB) models derived from human stem cells are powerful tools to improve our understanding of cerebrovascular diseases and to facilitate drug development for the human brain. Yet providing stem cell–derived endothelial cells with the right signaling cues to acquire BBB characteristics while also retaining their vascular identity remains challenging. Here, we show that the simultaneous activation of cyclic AMP and Wnt/β-catenin signaling and inhibition of the TGF-β pathway in endothelial cells robustly induce BBB properties in vitro. To target this interaction, we present a small-molecule cocktail named cARLA, which synergistically enhances barrier tightness in a range of BBB models across species. Mechanistically, we reveal that the three pathways converge on Wnt/β-catenin signaling to mediate the effect of cARLA via the tight junction protein claudin-5. We demonstrate that cARLA shifts the gene expressional profile of human stem cell–derived endothelial cells toward the in vivo brain endothelial signature, with a higher glycocalyx density and efflux pump activity, lower rates of endocytosis, and a characteristic endothelial response to proinflammatory cytokines. Finally, we illustrate how cARLA can improve the predictive value of human BBB models regarding the brain penetration of drugs and targeted nanoparticles. Due to its synergistic effect, high reproducibility, and ease of use, cARLA has the potential to advance drug development for the human brain by improving BBB models across laboratories.
2024-04-18 | GSE224846 | GEO
Project description:RNA sequencing of blood-brain barrier (BBB) microvessels from mice with hematogenous pneumococcal meningtis
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Project description:The blood-brain barrier (BBB) is a multicellular neurovascular unit (NVU) that allows the selective passage of necessary molecules into the central nervous system (CNS), while limiting the entry of neurotoxins and most drugs. A crosstalk with pericytes and neural cells mediates the acquisition of specialized properties, such as the formation of tight junctions (TJs), in brain microvascular endothelial cells (BMECs). TJs limit the paracellular passage of solutes, thereby regulating CNS homeostasis. However, the mechanisms by which NVU cells communicate to mediate TJ formation remains a mystery. Retinoic acid (RA), a key signaling molecule during vertebrate embryonic development, is commonly used to enhance functional barrier properties in in vitro BBB models. However, its physiological relevance and affected pathways are not fully understood.
2022-08-01 | GSE202485 | GEO
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
Project description:Nitrogen is a key factor impacting plant physiological processes and protein abundance. Although many proteins were changed substantially in poplar under N deficiency, the post-translational modifications in male and female poplars are still unclear. Therefore, we selected male and female poplars and analysed the changes of protein phosphorylation in response to N-deficient conditions.
2020-01-31 | PXD016397 | Pride