Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

SARS-CoV-2 infection of human pluripotent stem cell-derived vascular cells reveals smooth muscle cells as key mediators of vascular pathology during infection II

ABSTRACT: Nearly 20% of hospitalized patients diagnosed with severe SARS-CoV-2 infection are at risk for thromboembolic events. We developed a model of SARS-CoV-2 infection using human-induced pluripotent stem cell-derived endothelial cells, pericytes, and smooth muscle cells to recapitulate the vascular pathology associated with SARS-CoV-2 exposure. Our results demonstrate that perivascular cells, particularly smooth muscle cells (SMCs), are a specifically susceptible vascular target for SARS-CoV-2 infection. Utilizing RNA sequencing, we characterized the transcriptomic changes accompanying SARS-CoV-2 infection of SMCs, and endothelial cells (ECs). We observed that infected human SMCs shift to a pro-inflammatory state and increase the expression of key mediators of the coagulation cascade. Further, we showed human ECs exposed to the secretome of infected SMCs produce hemostatic factors that can contribute to vascular dysfunction, despite not being susceptible to direct infection. The findings here recapitulate observations from patient sera in human COVID-19 patients and provide mechanistic insight into the unique vascular implications of SARS-CoV-2 infection at a cellular level.

PROVIDER: GSE283152 | GEO | 2025/01/03

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

SARS-CoV-2 infection of human pluripotent stem cell-derived vascular cells reveals smooth muscle cells as key mediators of vascular pathology during infection

Project description:Nearly 20% of hospitalized patients diagnosed with severe SARS-CoV-2 infection are at risk for thromboembolic events. We developed a model of SARS-CoV-2 infection using human-induced pluripotent stem cell-derived endothelial cells, pericytes, and smooth muscle cells to recapitulate the vascular pathology associated with SARS-CoV-2 exposure. Our results demonstrate that perivascular cells, particularly smooth muscle cells (SMCs), are a specifically susceptible vascular target for SARS-CoV-2 infection. Utilizing RNA sequencing, we characterized the transcriptomic changes accompanying SARS-CoV-2 infection of SMCs, and endothelial cells (ECs). We observed that infected human SMCs shift to a pro-inflammatory state and increase the expression of key mediators of the coagulation cascade. Further, we showed human ECs exposed to the secretome of infected SMCs produce hemostatic factors that can contribute to vascular dysfunction, despite not being susceptible to direct infection. The findings here recapitulate observations from patient sera in human COVID-19 patients and provide mechanistic insight into the unique vascular implications of SARS-CoV-2 infection at a cellular level.

2025-01-08 | GSE240766 | GEO

Characterization of proteome dynamics in individual vascular layers at the early stage of acute sepsis

Project description:In this study we developed a stable isotope labeled of mammals (SILAM) model coupled to the application of differential systemic decellularization in vivo (DISDIVO) to evaluate the molecular dynamics of whole organism vascular beds at the initial phase of acute sepsis. Three different vascular layers where characterized at the initial stage of sepsis, glycocalyx (GC), endothelial cells (ECs) and smooth muscle cells (SMCs).

2020-10-29 | PXD018274 | Pride

Senescent endothelial cells are predisposed to SARS-CoV-2 infection and subsequent endothelial dysfunction

Project description:The coronavirus disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains to spread worldwide. COVID-19 is characterized by the striking high mortality in elderly; however, its mechanistic insights remain unclear. Systemic thrombosis has been highlighted in the pathogenesis of COVID-19, and lung microangiopathy in association with endothelial cells (ECs) injury has been reported by post-mortem analysis of the lungs. Here, we experimentally investigated the SARS-CoV-2 infection in cultured human ECs, and performed a comparative analysis for post-infection molecular events using early passage and replicative senescent ECs. We found that; 1) SARS-CoV-2 infects ECs but does not replicate and disappears in 72 hours without causing severe cell damage, 2) Senescent ECs are highly susceptible to SARS-CoV-2 infection, 3) SARS-CoV-2 infection alters various genes expression, which could cause EC dysfunctions, 4) More genes expression is affected in senescent ECs by SARS-CoV-2 infection than in early passage ECs, which might causes further exacerbated dysfunction in senescent ECs. These data suggest that sustained EC dysfunctions due to SARS-CoV-2 infection may contribute to the microangiopathy in the lungs, leading to deteriorated inflammation and thrombosis in COVID-19. Our data also suggest a possible causative role of EC senescence in the aggravated disease in elder COVID-19 patients.

2023-05-01 | GSE206677 | GEO

Next Generation Sequencing Analysis of human pluripotent stem cells derived endothelial and smooth muscle cells

Project description:Purpose: global gene expression profiling of H1 and iPSC derived endothelial cells (ECs) and smooth mucle cells (SMCs). Methods: SMART-seq2 amplified polyA RNA from undifferentiated H1 cells and iPSCs (in biological duplicates), cardiovascular progenitor cells, endothelial cells (ECs) and smooth muscle cells (SMCs) Results: Insulin free condition promoted cardiovascular mesoderm, endothelial and smooth muscle differentiation. Conclusions: the gene expression profiles of ECs and SMCs differentiated in insulin free medium confirmed that they are true ECs and SMCs.

2021-05-20 | GSE114776 | GEO

Organotypic Human Lung Bud Microarrays Identify BMP-dependent SARS-CoV-2 Infection in Lung Cells

Project description:Although lung disease is the primary clinical outcome in COVID-19 patients, how SARS-CoV-2 induces lung pathology remains elusive. Here we describe a high-throughput platform to generate self-organizing ad commensurate human lung buds derived from hESCs cultured on micropatterned substrates. Lung buds resemble human fetal lungs and display proximo-distal patterning of alveolar and airway tissue directed by KGF. These lung buds are susceptible to infection by SARS-CoV-2 and endemic coronaviruses and can be used to track cell type-specific cytopathic effects in hundreds of lung buds in parallel. Transcriptomic comparisons of infected lung buds and postmortem tissue of COVID-19 patients identified an induction of BMP signaling pathway. BMP activity renders lung cells more susceptible to SARS-CoV-2 infection and its pharmacological inhibition impairs infection by this virus. These data highlight the rapid and scalable access to disease-relevant tissue using lung buds that recapitulate key features of human lung morphogenesis and viral infection biology.

2023-02-21 | GSE225564 | GEO

Carnitine O-octanoyltransferase is a novel inducer of vascular calcification via promoting fatty acid metabolism and mitochondrial dysfunction

Project description:Objective – Vascular calcification is a critical pathology associated with increased cardiovascular event risk, but there are no FDA-approved anti-calcific therapies. We hypothesized and validated that an unbiased screening approach would identify novel mediators of human vascular calcification. Approach and Results – We performed an unbiased quantitative proteomics and pathway network analysis that identified increased carnitine O-octanoyltransferase (CROT) in calcifying primary human coronary artery smooth muscle cells (SMCs). Additionally, human carotid artery atherosclerotic plaques contained increased immunoreactive CROT near calcified regions. CROT siRNA reduced fibrocalcific response in calcifying SMCs. In agreement, histidine 327 to alanine point mutation inactivated human CROT fatty acid metabolism enzymatic activity and suppressed SMC calcification. CROT siRNA restored mitochondrial proteome alterations and suppressed mitochondrial fragmentation in calcifying SMCs. Lipidomics analysis of SMCs incubated with CROT siRNA revealed increased eicosapentaenoic acid, a vascular calcification inhibitor. CRISPR/Cas9-mediated Crot deficiency in low-density lipoprotein receptor-deficient mice reduced aortic and carotid artery calcification without altering bone density, or liver and plasma cholesterol and triglyceride concentrations. Conclusions – CROT is a novel inducer of vascular calcification via promoting fatty acid metabolism and mitochondrial dysfunction, as such CROT inhibition has strong potential as an anti-fibrocalcific therapy.

2021-02-26 | PXD022575 | Pride

Main Postoperative Complications After COVID-19

Project description:To explore the relationship between SARS-CoV-2 infection in different time before operation and postoperative main complications (mortality, main pulmonary and cardiovascular complications) 30 days after operation; To determine the best timing of surgery after SARS-CoV-2 infection.

| 5792 | ecrin-mdr-crc

A Retrospective Cohort Study for Main Postoperative Complications After SARS-CoV-2 Infection

| 12454 | ecrin-mdr-crc

Human cardiac pericytes are susceptible to SARS-CoV-2 infection

Project description:Coronavirus disease 2019 (COVID-19) is associated with serious cardiovascular complications, including myocarditis, thrombosis, and dysregulated hemodynamic responses. The mechanism(s) underlying these disease manifestations are incompletely understood. Given a critical role for pericytes in supporting endothelial cell health and maintaining vascular integrity, we hypothesized that infection of pericytes could explain some of the cardiovascular complications of COVID-19. Here, we present evidence of SARS-CoV-2 infection in cardiac pericytes in patients with COVID-19 myocarditis. We show that cardiac pericytes are permissive to SARS-CoV-2 infection in organotypic slice and primary cell cultures. SARS-CoV-2 enters cardiac pericytes through an ACE2 and endosomal-dependent mechanism. Consequences of cardiac pericyte infection include upregulation of inflammatory chemokine and cytokine expression, type I interferon signaling, mediators of endothelial constriction, and cell death. Collectively, these data demonstrate that human cardiac pericytes are susceptible to SARS-CoV-2 infection and suggest a possible role for pericyte infection in the pathogenesis of COVID-19.

2022-08-31 | GSE183850 | GEO

Identification of a novel risk factor for intracranial aneurysms in ADPKD using iPSC models [Agilent]

Project description:Cardiovascular complications are the leading cause of death in autosomal dominant polycystic kidney disease (ADPKD), and intracranial aneurysm (ICA) causing subarachnoid hemorrhage is among the most serious complications. The diagnostic and therapeutic strategies for ICAs in ADPKD have not been fully established. We here generated induced pluripotent stem cells (iPSCs) from seven ADPKD patients, including four with ICAs. The vascular cells differentiated from ADPKD-iPSCs showed altered Ca2+ entry and gene expression profiles compared with those from control-iPSCs. We found that the expression level of a metalloenzyme gene, matrix metalloproteinase (MMP) 1, was specifically elevated in the iPSC-derived endothelia from ADPKD patients with ICAs. Furthermore, we confirmed a statistically significant correlation between the serum MMP1 levels and the development of ICAs in 354 ADPKD patients, indicating that the serum MMP1 levels may be a novel risk factor and become more beneficial when combined with other risk factors. These results suggest that cellular disease models with ADPKD-specific iPSCs can be used to study the disease mechanisms and to identify novel disease-related molecules or risk factors. The gene expression profiles of vascular endothelia and smooth muscle cells derived from control- and ADPKD-iPSCs were analyzed. Seven control-iPSC derived endothelial cells (ECs), seven ADPKD-iPSC derived ECs, ten control-iPSC derived vascular smooth muscle cells (SMCs), and seven ADPKD-iPSC derived SMCs were analyzed.

2016-08-04 | E-GEOD-74451 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data