Transcriptome analysis after BBB-EC migration
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE255171 | GEO | 2024/02/11
REPOSITORIES: GEO
Similar Datasets
Project description:Endothelial cells (ECs) are constantly submitted in vivo to hemodynamical forces derived from the blood circulation, including shear stress (SS). EC are able to detect SS and consequently adapt their phenotype, thus affecting many endothelial functions. If a plethora of shear stress-regulated molecular networks have been described in peripheral EC, less is known about the molecular responses of microvascular brain ECs which constitute the blood-brain barrier (BBB). In this work, we investigated the response of human cerebral microvascular ECs to laminar physiological shear stress using the well characterized hCMEC/D3 cell line. Interestingly, we showed that hCMEC/D3 cells responded to shear stress by aligning perpendicularly to the flow direction, contrary to peripheral endothelial cells which aligned in the flow direction. Whole proteomic profiles were compared between hCMEC/D3 cells cultured either in static condition or under 5 or 10 dyn.cm-2 SS for three days. 3592 proteins were identified and expression levels were significantly affected for 3% of them upon both SS conditions. Pathway analyses were performed which revealed that most proteins overexpressed by SS refer to the antioxidant defense, probably mediated by activation of the NRF2 transcriptional factor. Regarding down-regulated proteins, most of them participate to the pro-inflammatory response, cell motility and proliferation. These findings confirm the induction of EC quiescence by laminar physiological SS and reveal a strong neuroprotective effect of SS on hCMEC/D3 cells, suggesting a similar effect on the BBB. Our results also showed that SS did not significantly increase expression levels nor did it affect the localization of junctional proteins or the functional activity of several ABC transporters (P-glycoprotein and MRPs). This work provides new insights on the response of microvascular brain EC to SS and on the importance of SS for optimizing in vitro BBB models.
2022-08-12 | PXD030493 | Pride
Project description:To identify in CNS endothelial cell (EC) the gene cohorts that participate in blood brain barrier (BBB) formation versus maintenance. We investigated mechanisms behind the reduced Wnt/β-catenin signaling observed in adult CNS ECs We also investigated whether the adult endothelial cells can re express the EC gene cohorts required for the BBB formation.
2022-11-03 | GSE214923 | GEO
Project description:To identify CNS endothelial cell (EC) the gene cohorts that participate in blood brain barrier (BBB) formation versus maintenance. We investigated mechanism behind the reduced Wnt/β-catenin signaling observed in adult CNS ECs We also investigated whether the adult endothelial cells can re express the EC gene cohorts required for the BBB formation.
2024-08-02 | GSE255967 | 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: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.
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2015-04-15 | MODEL1409240002 | BioModels
Project description:In the current study, we aimed to investigate the gene expression pattern in hCMEC/D3 cells using mRNA microarray analysis and to establish wheather hCMEC/D3 cells are a suitable in vitro human BBB model of neuroinflammation.
2013-09-16 | GSE45880 | GEO
Project description:We constructed one-cell stage embryos by maternal pronuclear (mPN) transfer having B6 ooplasm, B6 paternal PN (pPN), and either B6 or C3H mPN (BBB and BCB, respectively). We collected embryos of each type that were either treated (BBB+a, BCB+a) or untreated with α-amanitin (BBB, BCB) at the two-cell stage for microarray analysis. Comparison of the transcriptomes of these different kinds of embryos revealed genes for which expression differs according to maternal PN strain of origin, and the α-amanitin data revealed which of these differences is due to gene transcription, as opposed to any transcription-independent differences attributable to ooplasm-derived maternal mRNA pools. There are 4 replicates for each kind/treatment two-cell embryos (BBB, BCB, BBB+a, BCB+a).
2010-03-22 | E-GEOD-17886 | biostudies-arrayexpress
Project description:Comparison between EC and non-EC after EC purification in kidney and lung.
2010-06-05 | E-GEOD-711 | biostudies-arrayexpress