Transcriptome analysis of transplanted vascular organoid grafts under cranial window at the time of thrombosis after SARS-CoV-2 spike-ECD infusion
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA985596 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR24968456.fastq.gz | Fastqsanger.gz | |||
| SRR24968457.fastq.gz | Fastqsanger.gz | |||
| SRR24968458.fastq.gz | Fastqsanger.gz | |||
| SRR24968459.fastq.gz | Fastqsanger.gz | |||
| SRR24968460.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 6 |
Similar Datasets
Project description:We evaluated virus-induced damages in perfused human blood vessels from iPS-derived vascular organoid (iVO). By taking advantage of the cranial window model, iVOs were transplanted to develop human blood vessels by anastomosing the recipient mouse circulatory system. we infused SARS-CoV-2 spike protein (extracellular domain, ECD) in the mouse to determine the impact on chimeric human-mouse blood vessels formed under the cranial window. Our iVO transplantation studies indicated that Spike protein could specifically target human endothelial cells, but not murine endothelial cells, which leads to neutrophil migration by creating a coagulopathic milieu and therein generating microthrombi.
2023-10-05 | GSE235232 | GEO
Project description:Albeit vascular prostheses for the replacement of large arteries (e.g. aorta) are commercially available for decades, small-diameter vascular grafts (e.g., for coronary artery bypass graft surgery) still remain an unmet clinical need. Biostable polymers commonly used for the fabrication of aortic prostheses (e.g., poly(ethylene terephthalate) or expanded poly(tetrafluoroethylene)) have insufficient haemocompatibility to withstand thrombosis at low blood flow characteristic of small arteries (e.g., coronary artery). Hence, researchers endeavor to develop a biodegradable, tissue-engineered vascular graft (TEVG) to avoid the use of autologous blood vessels, such as saphenous vein or internal mammary artery, as conduits during the bypass surgery. Although a number of promising prototypes have been designed to date, none of them passed the pre-clinical trials successfully. Implantation into the ovine or porcine arteries is associated with thrombosis, neointimal hyperplasia, and aneurysms within one-year postoperation, precluding further clinical translation of TEVGs. Among the reasons of such impediment is that pathophysiology of TEVG implantation remains unclear and the molecular events occurring in the TEVG upon its implantation have not been properly investigated hitherto. Here, we for the first time performed a proteomic profiling of the TEVGs (n = 12) implanted into the ovine carotid arteries for one year and suffered from thrombosis to identify the signatures of TEVG failure in an unbiased manner. Contralateral intact ovine carotid arteries (n = 12) have been selected as a control group.
2022-11-26 | PXD036520 | Pride
Project description:Arterial and venous (A/V) thrombosis constitutes the greatest source of morbidity and mortality worldwide. Long considered as distinct entities, accumulating evidence indicates that A/V thrombosis can occur in the same populations suggesting that common mechanisms are likely operative. Although hyperactivation of the immune system is a common forerunner to the genesis of thrombotic events in both vascular systems, the key molecular control points remain poorly understood. Consequently, anti-thrombotic therapies targeting the immune system for therapeutic gain are lacking. Here we show that neutrophils are key effectors of both A/V thrombosis and can be targeted via novel immunoregulatory nanoparticles. Using antiphopholipid antibody syndrome (APS) as a model for devastating A/V thrombosis, we identified the transcription factor Krüppel-like factor 2 (KLF2) as a key regulator of neutrophil activation. Upon activation via genetic loss of KLF2 or administration of antiphospholipid antibodies, neutrophils cluster P-selectin glycoprotein ligand 1 (PSGL-1) via cortical actin remodeling, thereby increasing adhesion potential at thrombosis sites. Targeting clustered PSGL-1 using designer nanoparticles attenuates neutrophil-mediated A/V thrombosis in APS and KLF2 knockout models, illustrating the importance and feasibility of targeting activated neutrophils to prevent pathological thrombosis. Together, our results demosntrate a role for activated neutrophils to prevent pathological thrombosis. Together, our results demonstrate a role for activated neutorphils in both arterial and venous thrombosis and identify key molecular events that serve as potential targets for therapeutics against diverse causes of immunothrombosis.
2022-09-12 | GSE208336 | GEO
Project description:Liver transplantation is the only treatment option for patients with end-stage liver disease. However, a persistent disparity remains between supply and demand for donor organs suitable for transplantation, resulting in a waiting list mortality of up to 20%. This has resulted in an increasing use of high-risk grafts from suboptimal, extended criteria donors, including livers from donation after circulatory death (DCD) donors, and donors with significant comorbidities such as advanced age, diabetes mellitus and livers with high fat content. While cold storage remains sufficient for livers considered optimal for transplantation, ECD grafts are more vulnerable to cold ischemic damage, resulting in many of these grafts being rejected. As an alternative to cold storage, ex-situ normothermic machine perfusion (NMP) has become an increasingly popular method for preservation, transportation and assessment of ECD livers prior to transplantation. This allows for functional assessment of the graft and provides the opportunity to assess key processes that can be used to determine organ viability. The use of both hepatocellular and biliary viability criteria in selection of suboptimal livers from ECD donors has led to the successful transplantation of these grafts with a low incidence of post-transplant cholangiopathies. However, the mechanisms of biliary injury, and recovery thereof, following static cold storage remains poorly understood. Insight into these mechanisms may further improve preservation and selection of ECD livers. Therefore, we performed an in-depth proteomics analysis of bile samples collected from human ECD livers during NMP to identify potential mechanisms linked to biliary injury, function and regeneration over the course of the perfusion, and to assess whether biliary protein profiles can distinguish between transplantable and non-transplantable grafts.
2023-11-21 | PXD046355 | Pride
Project description:Because of inherent differences between deceased donor (DD) and living donor (LD) liver grafts, we hypothesize that the molecular signatures will be unique, correlating with specific biologic pathways and clinical patterns. Following reperfusion, 579 genes in DD grafts and 1324 genes in LDs were differentially expressed (p<0.005). Many up-regulated LD genes were related to regeneration, biosynthesis and cell cycle, and a large number of down-regulated genes were linked to hepatic metabolism and energy pathways correlating with post-transplant clinical laboratory findings. There was significant up-regulation of inflammatory/immune genes in both DD and LD, each with a distinct pattern. Gene expression patterns of select genes associated with inflammation and regeneration in LD and DD grafts correlated with protein expression. Unique patterns of early gene expression are seen in LD and DD liver grafts, correlating with protein expression and clinical results, demonstrating distinct inflammatory profiles and significant down-regulation of metabolic pathways in LD grafts. Experiment Overall Design: Microarray profiles of 63 biopsies in 13 DD and 8 LD liver grafts done at serial time points (procurement - No Manipulation, backbench - Cold Preservation, and 1-hour post-reperfusion - Post reperfusion) were compared between groups using class comparisons, network and biological function analyses. Specific genes were validated by quantitative PCR and immunopathology. Clinical findings were also compared.
2009-06-23 | E-GEOD-12720 | biostudies-arrayexpress
Project description:Deep vein thrombosis (DVT) is a common clinical problem, but its cellular and molecular mechanisms remain incompletely understood. We performed single-cell RNA sequencing (scRNA-seq) on the vein wall of mouse inferior vena cava (IVC) ligation model of deep vein thrombosis (DVT), to analyze the transcriptomic changes in the vein wall during acute venous thrombosis.
2023-02-10 | GSE221978 | GEO
Project description:GENEVA GWAS of Venous Thrombosis
| PRJNA75937 | ENA
Project description:Because of inherent differences between deceased donor (DD) and living donor (LD) liver grafts, we hypothesize that the molecular signatures will be unique, correlating with specific biologic pathways and clinical patterns. Following reperfusion, 579 genes in DD grafts and 1324 genes in LDs were differentially expressed (p<0.005). Many up-regulated LD genes were related to regeneration, biosynthesis and cell cycle, and a large number of down-regulated genes were linked to hepatic metabolism and energy pathways correlating with post-transplant clinical laboratory findings. There was significant up-regulation of inflammatory/immune genes in both DD and LD, each with a distinct pattern. Gene expression patterns of select genes associated with inflammation and regeneration in LD and DD grafts correlated with protein expression. Unique patterns of early gene expression are seen in LD and DD liver grafts, correlating with protein expression and clinical results, demonstrating distinct inflammatory profiles and significant down-regulation of metabolic pathways in LD grafts. Keywords: liver transplantation, live donor transplantation, liver regeneration, microarrays, mRNA expression, reperfusion injury
2009-06-11 | GSE12720 | GEO
Project description:Neutrophils play a pivotal role in the pathogenesis of lung ischemia-reperfusion injury. The effect of pro-resolving lipid mediators, such as Resolvin D1, on early neutrophil trafficking has not been assessed in organ transplantation. We obtained single-cell RNA sequencing of leukocytes from syngeneic left lung grafts to elucidate the genetic changes induced by recipient treatment with Resolvin D1 or vehicle.
2023-07-15 | GSE237110 | GEO
Project description:To identify insulin responsive genes in humans, in the first protocol, skeletal muscle biopsies from six non-diabetic subjects were obtained before and after a two-hour of hyperinsulinaemic (infusion rate 40 mU/m2/min) euglycemic clamp. A variable infusion of glucose (180 g/l) enriched with tritiated glucose (100 μCi/500 ml) maintained euglycemia during insulin infusion, with monitoring of plasma glucose concentration every 5 to 10 min during the basal and clamp periods using an automated glucose oxidation method (Glucose Analyzer 2, Beckman Instruments, Fullerton, CA). In the second protocol, skeletal muscle biopsies from six non-diabetic subjects were obtained before and after a 3-hour hyperinsulinemic (infusion rate 40 mU/m2/min) euglycemic clamp in order to increase the effects of insulin on gene expression. A variable infusion of glucose (180 g/l) was used to maintain euglycemia during insulin infusion with monitoring of plasma glucose concentration every 5 to 10 min using an automated glucose oxidation method (Glucose Analyzer 2, Beckman Instruments, Fullerton, CA). Keywords: dose response The muscle biopsies were obtained from the vastus lateralis muscle under local anesthesia before and after hyperinsulinaemic (infusion rate 40 mU/m2/min) euglycemic clamp
2007-03-01 | E-GEOD-7146 | biostudies-arrayexpress