Next Generation Sequencing Facilitates Quantitative Analysis of conventional and ischemia-free liver transplantation Transcriptomes
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE113024 | GEO | 2018/04/12
REPOSITORIES: GEO
Similar Datasets
Project description:Ischemia-reperfusion injury (IRI) remains the major reason for impaired donor graft function and increased mortality post-liver transplantation. The mechanism of IRI involves multiple pathophysiological processes and numerous types of cells. However, a systematic and comprehensive single-cell transcriptional profile of intrahepatic cells during liver transplantation is still unclear. We performed a single-cell transcriptome analysis of 14,313 cells from liver tissues collected from pre-procurement, at the end of preservation and 2 h post-reperfusion. We made detailed annotations of mononuclear phagocyte, endothelial cell, NK/T, B and plasma cell clusters, and we described the dynamic changes of the transcriptome of these clusters during IRI and the interaction between mononuclear phagocyte clusters and other cell clusters. In addition, we found that TNFAIP3 interacting protein 3 (TNIP3), specifically and highly expressed in Kupffer cell clusters post-reperfusion, may have a protective effect on IRI. In summary, our study provides the first dynamic transcriptome map of intrahepatic cell clusters during liver transplantation at single-cell resolution.
2021-04-07 | GSE171539 | GEO
Project description:INTRODUCTION Ischemia and reperfusion injury (IRI)-elicited tissue injury contributes to morbidity and mortality in a wide range of pathologies, including myocardial infarction, ischemic stroke, acute kidney injury, trauma, circulatory arrest 1. Ischemia-reperfusion injury is also a major challenge during organ transplantation and cardiothoracic, vascular and general surgery 1. IRI, one of the biggest challenges for organ transplantation, continues to be a vital source of morbidity among recipients, especially in liver transplantation 2. With the enlarging shortage of available donor livers, the increased use of extended criteria donor grafts further increases IRI, adversely affecting both short-term and long-term outcomes of graft and patient survival 3. Numerous studies have investigated the benefits of pharmacological, heat shock, and ischemic preconditioning interventions aimed at decreasing liver IRI 4. However, the benefit was limited. Our center has been making great effort in conquering IRI and have developed a novel surgical technique called ischemia-free liver transplantation 5. It is an ultimate method to overcome IRI in liver transplantation, but there is still a long way to popularize it. As a result, it is still of great significance to study IRI and identify the core genes in the process and the underlying mechanism. Comprehensive bioinformatics analysis has been increasingly important as a method to study various pathological and physiological condition 6. By enrolling multiple omics or combining different types of omics, comprehensive bioinformatics analysis was able to recognize key factors that could have potentially pathogenic impact such as gene expression, protein function, and downstream pathways. With the rapid development of high-throughput sequencing technologies, several transcriptomic datasets on IRI of liver transplantation have become available in the Gene Expression Omnibus (GEO) database. Herein, we recruited 3 GEO datasets to conduct comprehensive analysis with the GEO dataset from our center. Moreover, we performed the first proteome of liver tissues to study liver IRI. Then the transcriptome and proteome were used for combined analysis to reveal key factors in liver IRI.
2022-02-23 | PXD010812 | Pride
Project description:Ischemia reperfusion injury (IRI) in organ transplantation remains a significant problem with limited alternative therapeutic options. Organs that undergo significant damage during IRI, particularly those enduring long warm ischemia times, undergo significant delayed graft function (DGF) after reperfusion and tend to have greater complications long term with the onset of chronic rejection. The gas molecule carbon monoxide (CO) has emerged as an agent that can suppress IRI in rodent models of solid organ transplantation. Since the use of CO is a potential therapeutic modality in humans, we tested if CO can prevent DGF in a pig model of kidney transplantation Keywords: stress response, treatment response 18 Samples from pig kidneys, two naïve controls, two timepoints, two conditions, 4 replicates
2009-01-20 | E-GEOD-14373 | biostudies-arrayexpress
Project description:Ischemia reperfusion injury (IRI) in organ transplantation remains a significant problem with limited alternative therapeutic options. Organs that undergo significant damage during IRI, particularly those enduring long warm ischemia times, undergo significant delayed graft function (DGF) after reperfusion and tend to have greater complications long term with the onset of chronic rejection. The gas molecule carbon monoxide (CO) has emerged as an agent that can suppress IRI in rodent models of solid organ transplantation. Since the use of CO is a potential therapeutic modality in humans, we tested if CO can prevent DGF in a pig model of kidney transplantation Keywords: stress response, treatment response
2009-01-20 | GSE14373 | GEO
Project description:BACKGROUND: Hypovolemia is common in lung donors before or after brain death. However, its impact on primary graft function (PGD) remains obscure. METHODS: A clinically relevant two-hit model of PGD was established by integrating hypovolemic shock (HS) and cold ischemia-reperfusion in a mouse model of orthotopic lung transplantation (LTx) from C57BL/6 to Balb/c. At -48 hours, HS was induced to donor by withdrawal of blood from femoral artery and keeping the mean arterial pressure at 15±5 mmHg for 4 h. At -24 hours, donor lungs were retrieved from mice with or without HS and stored at 0ºC until transplantation. CD11b-DTR mice were used as donor and treated with Diphtheria Toxin (DT) to deplete graft-infiltrating macrophages. RESULTS: HS mainly caused macrophage-predominant infiltration around pulmonary artery injury systemic inflammatory response, but little impairment of lung function even if in combination with cold ischemia-reperfusion. Transcriptional profiling showed HS pretreatment increased pulmonary damage and alveolar remodeling but ameliorated inflammatory infiltration when compared to one-hit model of 12 hours cold ischemia-reperfusion injury. The allografts with donor DT-treatment one day ahead of HS showed injury and dysfunction at donation and worsened further at 24 hours reperfusion, whereas the allografts with recipient DT-treatment immediately after transplantation showed similar function and histology to the control treated with saline. CONCLUSION: Donor hypovolemia causes pulmonary artery injury and infiltration but has little impact on allograft function, even in combination with 24 h cold ischemia. Graft-infiltrating macrophages are critical in protecting graft from HS-induced injury and cold ischemia-reperfusion injury.
2022-03-30 | GSE156322 | GEO
Project description:Our understanding on mechanisms of ischemia-reperfusion induced lung injury during lung preservation and transplantation is based on clinical observations and animal studies. Herein, we used cell and systems biology approaches to explore these mechanisms at transcriptomics levels, especially by focusing on the differences between human lung endothelial and epithelial cells, which are crucial for maintaining essential lung structure and function. Human pulmonary microvascular endothelial cells and human lung epithelial cells were cultured to confluent, subjected to different cold ischemic time (CIT) to mimic static cold storage with preservation solution, and then subjected to warm reperfusion with serum containing culture medium to similar lung transplantation. Cell morphology, viability and transcriptomic profiles were studied. Ischemia-reperfusion induced a CIT time-dependent cell death, which was associated with dramatic changes in gene expression. Under normal control conditions, endothelial cells showed gene clusters enriched in vascular process and inflammation, while epithelial cells showed gene clusters enriched in protein biosynthesis and metabolism. CIT 6 h alone or after reperfusion had little effects on these phenotypic characteristics. After CIT 18 h, protein biosynthesis related gene clusters disappeared in epithelial cells; after reperfusion, metabolism-related gene cluster in epithelial cells and multiple gene clusters in the endothelial cells also disappeared. Human pulmonary endothelial and epithelial cells have distinct phenotypic transcriptomic signatures. Severe cellular injury reduces these gene expression signatures in a cell type dependent manner. Therapeutics that preserve these transcriptomic signatures may represent new treatment to prevent acute lung injury during lung transplantation.
2021-04-17 | GSE172222 | GEO
Project description:Ischemia/reperfusion injuries is a known complication to hepatic surgery. Ischemic pre- (IPC) and postconditioning (IPO) protects the liver against ischemia/reperfusion-injuries. Expression profiling were performed on liver biopsies seeking to identify molecular mediators of the protective properties. 48 rats were divided into 5 groups; sham (n=8), IRI (n=10), IPC (n=10), IPO (n=10) and IPC+IPO (n=10). All rats except sham rats were subjected to 30 min of total liver ischemia and 30 min of reperfusion before liver biopsies were sampled. In the IPC group, liver ischemia was preceded by 10 min of hepatic ischemia, followed by 10 min of reperfusion. IPO were performed by three cycles of 30 sec of reperfusion and 30 sec of ischemia, applied immediately after the 30 min of total liver ischemia. In the IPC+IPO group the two interventions were combined.
2011-09-30 | E-GEOD-24430 | biostudies-arrayexpress
Project description:Inflammatory responses, apoptosis, and oxidative stress, are key factors that contribute to hepatic ischemia/reperfusion (I/R) injury, which may lead to the failure of liver surgeries, such as hepatectomy and liver transplantation. The N6-methyladenosine (m6A) modification has been implicated in multiple biological processes, and its specific role and mechanism in hepatic I/R injury require further investigation. We found that METTL3 may be involved in regulating this process. Therefore, we constructed an ischemia-reperfusion model with Hepatocyte-specific METTL3 knockdown (HKD) mice, and performed RNA- sequencing analysis with wild-type mice as controls.
2024-04-22 | GSE252255 | GEO
Project description:Ischemia-reperfusion injury (IRI) is a major cause of morbidity and mortality following conventional lung transplantation and warm ischemia may limit success of transplanting lungs from non-heart-beating donors. We sought to determine alterations in gene expression in rat lung tissue subjected to warm ischemia in vivo followed by reperfusion. Keywords: time course
2019-04-30 | GSE9634 | GEO
Project description:Acute cellular rejection occurs frequently during the first few weeks following liver transplantation. During this period its molecular phenotype is confounded by pro-inflammatory events elicited by surgery, ischemia-reperfusion injury and early post-transplant complications. To unambiguously define the molecular profile associated with rejection we collected sequential biological specimens from liver transplant patients at least 3 years after transplantation who developed rejection while enrolled in trials of intentional immunosuppression withdrawal Transcriptomic RISET 2.0 chips were employed using portal blood vein from 37 liver trasplant patients.Two timepoints were selected: before immunosupressive weaning and rejection time point.
2016-06-01 | E-GEOD-70305 | biostudies-arrayexpress