Transcriptional Responses of in vitro Blood-Brain Barrier Models to Shear Stress
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1162799 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR30723400_1.fastq.gz | Fastqsanger.gz | |||
| SRR30723400_2.fastq.gz | Fastqsanger.gz | |||
| SRR30723375_1.fastq.gz | Fastqsanger.gz | |||
| SRR30723375_2.fastq.gz | Fastqsanger.gz | |||
| SRR30723376_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 52 |
Similar Datasets
Project description:Endothelial cells throughout the body sense blood flow, eliciting transcriptional and phenotypic responses. Brain endothelium, known as the blood-brain barrier (BBB), possesses unique barrier and transport properties which are in part regulated by blood flow. We utilized next generation sequencing to analyze the transcriptome of primary cultured rat brain microvascular endothelial cells (BMECs) as well as three human induced pluripotent stem cell-derived models. We compared the transcriptional responses of these cells to either low (~0.5 dyne/cm2) or high (12 dyne/cm2) shear stresses, and subsequent analysis identified genes and pathways that were influenced by shear including key BBB-associated genes (SLC2A1, LSR, PLVAP) and canonical endothelial shear stress response transcription factors (KLF2, KLF4). In addition, our analysis suggests that shear alone is insufficient to rescue de-differentiation caused by in vitro primary BMEC culture. Overall, these datasets and analyses provide new insights into the role of shear on BBB models that will aid in model selection and guide further model development.
2025-03-05 | GSE277559 | GEO
Project description:Endothelial cells throughout the body sense blood flow, eliciting transcriptional and phenotypic responses. The brain endothelium, known as the blood-brain barrier (BBB), possesses unique barrier and transport properties, which are in part regulated by blood flow. We utilized RNA sequencing to analyze the transcriptome of primary cultured rat brain microvascular endothelial cells (BMECs), as well as three human induced pluripotent stem cell-derived models. We compared the transcriptional responses of these cells to either low (0.5 dyne/cm2) or high (12 dyne/cm2) shear stresses, and subsequent analyses identified genes and pathways that were influenced by shear including key BBB-associated genes (SLC2A1, LSR, PLVAP) and canonical endothelial shear-stress-response transcription factors (KLF2, KLF4). In addition, our analysis suggests that shear alone is insufficient to rescue the de-differentiation caused by in vitro primary BMEC culture. Overall, these datasets and analyses provide new insights into the influence of shear on BBB models that will aid in model selection and guide further model development.
| S-EPMC11853657 | biostudies-literature
Project description:Silver nanoparticles (AgNP) have been reported to penetrate the central nervous system and induce neurotoxicity. However, there is paucity in understanding the toxicity of AgNPs and their effect on the blood-brain barrier (BBB) including the underlying molecular mechanism(s) of action. Using an in vitro BBB model and mass spectrometry based proteomics we investigated the alteration in the proteome pathways of the brain endothelial cells and astrocytes exposed to AgNPs for 24 and 48 hours.
2018-11-07 | PXD009197 | Pride
Project description:Influence of substrate stiffness on barrier function in an iPSC-derived in vitro blood-brain barrier model
| PRJEB44183 | ENA
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:Drug-induced nephrotoxicity is a leading cause of drug attrition, partly due to the limited relevance of pre-clinical models of the proximal tubule. Culturing proximal tubule epithelial cells (PTECs) under fluid flow to mimic physiological shear stress has been shown to improve select phenotypes, but existing flow systems are expensive and difficult to implement by non-experts in microfluidics. Here, we designed and fabricated an accessible and modular flow system for culturing PTECs under physiological shear stress, which induced native-like cuboidal morphology, downregulated pathways associated with hypoxia, stress, and injury, and upregulated xenobiotic metabolism pathways. We also compared the expression profiles of shear-dependent genes in our in vitro PTEC tissues to that of ex vivo proximal tubules and observed stronger clustering between ex vivo proximal tubules and PTECs under physiological shear stress relative to PTECs under negligible shear stress. Together, these data illustrate the utility of our user-friendly flow system and highlight the role of shear stress in promoting native-like morphological and transcriptomic phenotypes in PTECs in vitro, which is critical for developing more relevant pre-clinical models of the proximal tubule for drug screening or disease modeling.
2022-12-31 | GSE221871 | GEO
Project description:Neutrophil-derived microvesicle induced dysfunction of the blood-brain barrier in vitro
| PRJNA564567 | ENA
Project description:In this study, we characterized the adaptive response of arterial endothelial cells to acute increases in shear stress magnitude in well-defined in vitro settings. Porcine endothelial cells were preconditioned by a basal level shear stress of 15 ± 15 dynes/cm2 at 1 Hz for 24 hours, and an acute increase in shear stress magnitude (30 ± 15 dynes/cm2) was then applied. The transcriptomics studies using microarray identified genes that were sensitive to the elevated shear magnitude. A significant number of the identified genes in our study are previously unknown as sensitive to shear stress. Porcine endothelial cells were preconditioned by a basal level shear stress of 15 ± 15 dynes/cm2 at 1 Hz for 24 hours, and an acute increase in shear stress magnitude (30 ± 15 dynes/cm2) was then applied. Gene expression at multiple time points was measured using microarray.
2011-12-01 | E-GEOD-26505 | biostudies-arrayexpress
Project description:We are interested in the role of NOTCH1 and Shear Stress in Aortic Valve Endothelium. Primary human aortic valve endothelium was subjected to 4 conditions in vitro. 1) Control siRNA, No shear stress. 2) NOTCH1 siRNA, No shear stress. 3) Control siRNA, 15 dynes/cm2 shear stress. 4) NOTCH1 siRNA, 15 dynes/cm2 shear stress. Triplicates of each condition were pooled for library perp and sequencing
2015-05-16 | E-GEOD-47157 | biostudies-arrayexpress
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