RNAseq of human brain cell lines
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE160149 | GEO | 2021/04/23
REPOSITORIES: GEO
Similar Datasets
Project description:The aim of the present work was to investigate the effect of monensin on the in vitro growth of T. gondii tachyzoites and on the host cells (human brain microvascular endothelial cells - hBMECs). The hypotheses were that (1) inhibition of the WNT signalling pathway by monensin can reduce the growth of T. gondii infecting human brain microvascular endothelial cells (hBMECs) and (2) by suppression of the growth of T. gondii using monensin, impairment of the BBB integrity can be restored (3) inhibition of WNT pathway by monensin can be detected by microarray experiment.
2020-07-06 | E-MTAB-8817 | biostudies-arrayexpress
Project description:Qosa2014 - Mechanistic modeling that
describes Aβ clearance across BBB
Qosa2014 - Mechanistic modeling that
describes Aβ clearance across BBB.
Encoded non-curated model. Issues:
- Confusing equation 6
- Missing initial values for spices
This model is described in the article:
Differences in amyloid-?
clearance across mouse and human blood-brain barrier models:
kinetic analysis and mechanistic modeling.
Qosa H, Abuasal BS, Romero IA,
Weksler B, Couraud PO, Keller JN, Kaddoumi A.
Neuropharmacology 2014 Apr; 79:
668-678
Abstract:
Alzheimer's disease (AD) has a characteristic hallmark of
amyloid-? (A?) accumulation in the brain. This accumulation of
A? has been related to its faulty cerebral clearance. Indeed,
preclinical studies that used mice to investigate A? clearance
showed that efflux across blood-brain barrier (BBB) and brain
degradation mediate efficient A? clearance. However, the
contribution of each process to A? clearance remains unclear.
Moreover, it is still uncertain how species differences between
mouse and human could affect A? clearance. Here, a modified
form of the brain efflux index method was used to estimate the
contribution of BBB and brain degradation to A? clearance from
the brain of wild type mice. We estimated that 62% of
intracerebrally injected (125)I-A?40 is cleared across BBB
while 38% is cleared by brain degradation. Furthermore,
in vitro and in silico studies were performed to compare
A? clearance between mouse and human BBB models. Kinetic
studies for A?40 disposition in bEnd3 and hCMEC/D3 cells,
representative in vitro mouse and human BBB models,
respectively, demonstrated 30-fold higher rate of (125)I-A?40
uptake and 15-fold higher rate of degradation by bEnd3 compared
to hCMEC/D3 cells. Expression studies showed both cells to
express different levels of P-glycoprotein and RAGE, while LRP1
levels were comparable. Finally, we established a mechanistic
model, which could successfully predict cellular levels of
(125)I-A?40 and the rate of each process. Established
mechanistic model suggested significantly higher rates of A?
uptake and degradation in bEnd3 cells as rationale for the
observed differences in (125)I-A?40 disposition between mouse
and human BBB models. In conclusion, current study demonstrates
the important role of BBB in the clearance of A? from the
brain. Moreover, it provides insight into the differences
between mouse and human BBB with regards to A? clearance and
offer, for the first time, a mathematical model that describes
A? clearance across BBB.
This model is hosted on
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MODEL1409240002.
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2015-04-15 | MODEL1409240002 | BioModels
Project description:Our study showed that fibroblasts significantly attenuated blood-brain barrier (BBB) disruption in an in vitro intracerebral hemorrhage (ICH) model. Since fibroblasts and brain microvascular endothelial cells were not in direct contact in this model, we reasoned that fibroblasts did so by secreting molecules with BBB-protective function. Here, we further screened fibroblast-secreted molecules in this in vitro ICH model by mass spectrometry.
2022-11-14 | PXD037247 | Pride
Project description:Understanding the cellular origin and differentiation status of glioblastoma is critical to resolve the etiology of the disease. we profile control and genetically modified human brain perivasuclar fibroblasts by single cell RNA sequencing (scRNAseq). From this, we observed the potential tumorigenicity of brian perivascular fibroblasts.
2022-04-19 | GSE171287 | 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:Human cerebral malaria (HCM) is a severe complication of Plasmodium falciparum (P.f.) infection that is characterized by capillary occlusions, rupture of the blood-brain barrier (BBB) and perivascular cellular injury. P.f. histidine-rich protein 2 (HRP2), a byproduct of parasitized red blood cell (pRBC) lysis, crosses the BBB when compromised to cause brain injury. We hypothesized that HRP2-induced neuronal damage can be attenuated by Neuregulin 1 (NRG1), an anti-inflammatory neuroprotective factor. Using brain cortical organoids, we determined that HRP2 upregulated cell death and inflammatory markers and disorganized brain organoid tissue. We identified Toll Like Receptors (TLR1 and 2) as potential mediators of HRP2-induced cellular damage and inflammation. Exogenous treatment of organoids with NRG1 attenuated HRP2 effects. The results indicate that HRP2 mediates malaria-associated HRP2-induced brain injury and inflammation and that NRG1 may be an effective therapy against HRP2 effects in the brain. In the study presented here, we assessed the inflammatory genes induced by HRP2 using the Immunology Panel on the nCounter system (NanoString) and results were analyzed using nSolver softaware.
2022-06-08 | GSE190750 | GEO
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 blood-brain barrier (BBB) dynamically controls and maintains a precisely balanced brain microenvironment necessary for reliable functioning. It is made up of highly specialized endothelial cells (ECs) in the lining of the vascular wall. These ECs are surrounded by the basal lamina, astrocytic perivascular endfeet, pericytes, microglia and neuronal processes that have been shown to contribute to barrier function1. In essence, the brain endothelium limits both transcellular and paracellular passage of cells and molecules into the central nervous system (CNS). Transcellular passage of hydrophilic molecules is limited due to a low rate of transcytotic vesicles, an extremely low pinocytotic activity, expression of active efflux transporters, and high metabolic activity. Paracellular diffusion of hydrophilic molecules and trafficking of immune cells is restricted by a network of tight junctions (TJs)2-5. Due to these characteristics, the BBB is able to protect the CNS from sudden changes in blood composition and uncontrolled influx of immune cells. In a large number of neuro-inflammatory diseases, an impaired function and an opening of the BBB are observed. In diseases of the CNS like multiple sclerosis or stroke or after brain trauma, the BBB becomes inflamed (mediated by for example reactive oxygen species (ROS) and hypoxia) and its function severely impaired which gives rise to enhanced cellular infiltration, thus contributing to tissue damage and neurological deficits. Due to the specialized nature of brain ECs, transmigration of leukocytes through cerebrovascular endothelium is likely to differ from that in other vascular beds. Generally, the transmigration process is closely controlled by the interaction of leukocytes with the endothelial surface followed by low velocity rolling, arrest, firm adhesion, and finally transmigration. For the diapedesis of immune cells across the cerebral vasculature a re-arrangement of the cytoskeleton and opening of the TJ complexes is required to allow cells to pass into the sub endothelial space. In the initial step of the adhesive cascade leukocytes adhere to the endothelium with low affinity. This adhesion is mediated by several members of the selectin family and their corresponding ligands. Despite the low affinity of these interactions, resulting contact of leukocytes with the endothelium leads to further activation of both cell types and finally transmigration of the leukocytes through the BBB6,7. The glycosylation of endothelial cells of different vascular bed origins To date it is unknown which specific carbohydrate structures on the BBB endothelium mediate leukocyte capture and rolling, and whether these structures are differentially expressed onto inflamed brain EC compared to normal brain ECs and vascular beds of other organs. Initial studies using qPCR and FACS analysis within our group reveal that brain endothelial cells have a different profile in their glycosylation-related genes compared to microvascular ECs upon inflammation, which may result in a different glycosylation profile of adhesive structures and may underlie rolling, adhesion and diapedesis of leukocytes. In this project we wish to identify specific, glycosylated structures on brain endothelial cells that mediate capture, rolling and diapedesis of leukocytes in the brain. To investigate the expression of glycosyltransferases in dendritic cells and the changes in expression associated with maturation. RNA preparations from stimulated and non-stimulated hcMEC/D3 (human brain endothelial cells line) and FMVEC (human promary microvascular endothelial cells isolated from foreskins) were sent to both Microarray Core (E) and Core(C). The RNA was put on an RNeasy Column, amplified, labeled, and hybridized to the Glycov3 microarrays. Data was sent to Dr. van Kooyk's lab for analysis.
2011-06-14 | E-GEOD-29932 | biostudies-arrayexpress
Project description:Using mice with targeted gene mutations, we identify (1) distinct roles for different canonical Wnt signaling components in central nervous system (CNS) vascular development and in the specification of the blood-brain and blood-retina barriers (BBB and BRB) and (2) differential sensitivities of the vasculature in various CNS regions to perturbations in canonical Wnt signaling components. We find nearly equivalent roles for Lrp5 and Lrp6 in brain vascular development and barrier maintenance but a dominant role for Lrp5 in the retinal vasculature, an especially high sensitivity of the BBB in the cerebellum and pons/interpeduncular nuclei to decrements in canonical Wnt signaling, and plasticity in the barrier properties of mature CNS vasculature. Brain and retinal vascular defects caused by loss of Norrin/Frizzled4 signaling can be fully rescued by stabilizing beta-catenin, and loss of beta-catenin’s transcriptional activation domain or expression of a dominant negative Tcf4 recapitulates the vascular development and barrier defects seen with loss of receptor, co-receptor, or ligand, indicating that Norrin/Frizzled4 signaling acts predominantly by beta-catenin-dependent transcriptional regulation. This work strongly supports a model in which identical or nearly identical canonical Wnt signaling mechanisms mediate neural tube and retinal vascularization and maintain the BBB and BRB. Total retina RNA from P10 WT, NdpKO, Ctnnb1flex3/+;Pdgfb-CreER, and NdpKO;Ctnnb1flex3/+;Pdgfb-CreER mice was subjected to RNAseq
2014-06-05 | E-GEOD-56461 | biostudies-arrayexpress