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SARS-CoV-2 causes dysfunction in human iPSC-derived brain microvascular endothelial like cells potentially by signal modulation

ABSTRACT: SARS-CoV-2 causes dysfunction in human iPSC-derived brain microvascular endothelial like cells potentially by signal modulation

PROVIDER: PRJNA1069682 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR27742944_1.fastq.gz	Fastqsanger.gz
	SRR27742944_2.fastq.gz	Fastqsanger.gz
	SRR27742945_1.fastq.gz	Fastqsanger.gz
	SRR27742945_2.fastq.gz	Fastqsanger.gz

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SARS-CoV-2 causes dysfunction in human iPSC-derived brain microvascular endothelial like cells potentially by signal modulation

Project description:SARS-CoV-2 is considered to affect the central nervous system (CNS) by interacting with the blood–brain barrier (BBB), which is defined by tight junctions that seal paracellular gaps between brain microvascular endothelial like cells (BMECs). Although SARS-CoV-2 infection of BMECs has been reported, the mechanism has not been fully elucidated. Here, we investigated the mechanism using iPSC derived brain microvascular endothelial like cells (iPSC-BMELCs). We observed that iPSC-BMELCs were infected with SARS-CoV-2, which resulted in inflammatory responses. RNA-seq analysis revealed that SARS-CoV-2 modulated the expression of signal molecules in iPSC-BMELCs. These findings suggest that SARS-CoV-2 infection causes BBB dysfunction in humans.

2024-02-01 | GSE254309 | GEO

mRNAseq of Huntington's disease and control patient iPSC-derived brain microvascular endothelial cells

Project description:Purpose: The goals of this study are to compare the transcriptomic profile (mRNA-seq) of HD and control patient iPSC-derived brain microvascular endotheial cells to identify alterations in gene expression. Methods: RNA were isolated from HD and control iPSC-derived brain microvascular endothelial cells. mRNAseq using Illumina TruSeq mRNA PolyA+ v2 lib prep and HiSeq 2500. Statistical difference in mRNA levels were calculated with subsequent GO and pathway analysis. Results: mRNAseq and statistical analysis revealed differentially expressed genes between HD and control iPSC-derived brain microvascular endothelial cells. Conclusions: Our study shows differentially expressed genes between HD and control iPSC-derived brain microvascular endothelial cells, and reveals gene networks that are relevant to the mechanism of HD pathogenesis.

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RNA-seq expression data from Human iPSC-derived Brain Microvascular Endothelial-like Cells (iBMECs)

Project description:Comparison of Human iPSC-derived Brain Microvascular Endothelial-like Cells (iBMECs) grown in poly(dimethylsiloxane) tissue chips. Data contains RNA-seq profiles of iBMECs exposed to various levels of shear stress ranging from 0, 0.01, 0.5, and 2.4 dyn/cm2; as well as RNA-seq profiles of FACS sorted iBMECs cultured alone or with primary human astrocytes and pericytes or with iPSC-derived neural progenitor cells.

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RNA sequencing of human iPSC-derived brain microvascular endothelial cells.

Project description:RNA sequencing of human iPSC-derived brain microvascular endothelial cells.

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RNA-sequencing of brain microvascular endothelial cell dysfunction in an isogenic juvenile iPSC model of Huntington’s disease

Project description:Huntington's disease (HD) is associated with dysfunction of the blood-brain barrier, including brain microvasscular endothelial cells (BMECs). We report changes in gene expression of induced pluripotent stem cells (iPSCs) and iPSC-derived brain microvascular endothelial cell-like cells (iBMECs) derived from an isogenic pair of iPSCs with either 180 (HD-corrected) or 18 (HD180) CAG repeats in the HTT gene.

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SARS-CoV-2 causes dysfunction in human iPSC-derived brain microvascular endothelial cells potentially by modulating the Wnt signaling pathway.

Project description:BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), which is associated with various neurological symptoms, including nausea, dizziness, headache, encephalitis, and epileptic seizures. SARS-CoV-2 is considered to affect the central nervous system (CNS) by interacting with the blood-brain barrier (BBB), which is defined by tight junctions that seal paracellular gaps between brain microvascular endothelial cells (BMECs). Although SARS-CoV-2 infection of BMECs has been reported, the detailed mechanism has not been fully elucidated.MethodsUsing the original strain of SARS-CoV-2, the infection in BMECs was confirmed by a detection of intracellular RNA copy number and localization of viral particles. BMEC functions were evaluated by measuring transendothelial electrical resistance (TEER), which evaluates the integrity of tight junction dynamics, and expression levels of proinflammatory genes. BMEC signaling pathway was examined by comprehensive RNA-seq analysis.ResultsWe observed that iPSC derived brain microvascular endothelial like cells (iPSC-BMELCs) were infected with SARS-CoV-2. SARS-CoV-2 infection resulted in decreased TEER. In addition, SARS-CoV-2 infection decreased expression levels of tight junction markers CLDN3 and CLDN11. SARS-CoV-2 infection also increased expression levels of proinflammatory genes, which are known to be elevated in patients with COVID-19. Furthermore, RNA-seq analysis revealed that SARS-CoV-2 dysregulated the canonical Wnt signaling pathway in iPSC-BMELCs. Modulation of the Wnt signaling by CHIR99021 partially inhibited the infection and the subsequent inflammatory responses.ConclusionThese findings suggest that SARS-CoV-2 infection causes BBB dysfunction via Wnt signaling. Thus, iPSC-BMELCs are a useful in vitro model for elucidating COVID-19 neuropathology and drug development.

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RNA sequencing of human iPSC-derived brain microvascular endothelial cells.

Project description:Induced pluripotent stem cells were differentiated to brain microvascular endothelial cells (BMECs) using previously published protocols with minor changes. RNA was collected from purified BMECs after barrier induction and submitted for sequencing.

2020-12-31 | E-MTAB-8802 | biostudies-arrayexpress

RNA-seq expression data from Human iPSC-derived Brain Microvascular Endothelial-like Cells (iBMECs)

Project description:RNA-seq expression data from Human iPSC-derived Brain Microvascular Endothelial-like Cells (iBMECs)

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