Resolving the graft ischemia-reperfusion injury during liver transplantation at the single cell resolution
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ABSTRACT:
PROVIDER: PRJNA719997 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR14150307_1.fastq.gz | Fastqsanger.gz | |||
| SRR14150307_2.fastq.gz | Fastqsanger.gz | |||
| SRR14150308_1.fastq.gz | Fastqsanger.gz | |||
| SRR14150308_2.fastq.gz | Fastqsanger.gz | |||
| SRR14150309_1.fastq.gz | Fastqsanger.gz |
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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: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:Ischemia reperfusion (IR) is an unavoidable step of organ transplantation. IR-induced injury constrains the number of donor lungs used for transplant. Here we performed longitudinal single-cell RNA sequencing (scRNA-seq) from human lungs of six individuals who underwent lung transplantation. Lung biopsies were collected after cold preservation and 2-hour reperfusion for each individual resulting in the profiling of 108,613 cells in total.
2024-10-12 | GSE220797 | 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) 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:Cold ischemia-reperfusion induced injury contributes to poor lung transplant outcomes. We used transcriptome sequencing to study the biological response of mouse lungs to the cold ischemia-reperfusion process. Mouse orthotopic left LTx was performed with standard cuff techniques. Briefly, the donor lungs were recovered after being flushed with 10ml low potassium dextran (LPD) solution and inflated with 50% oxygen. Cold ischemia was induced by storing donor lungs in 20ml LPD at 4°C for 24 hours. Then, the left donor lung was cuffed and implanted into recipients within 45 minutes. After the 4-hour reperfusion, the recipient mice were sacrificed and the transplanted lungs were collected.
2023-01-20 | GSE222957 | GEO
Project description:Ischemia-reperfusion (IR) injury, a ubiquitous consequence of liver transplantation, is a cause of early graft rejection and increased morbidity. At present, there are no effective strategies to reduce hepatic IR injury. Molecular mechanisms that promote cell survival under these circumstances are largely undefined. We examined changes in global gene expression at early reperfusion times to identify potential IR-mediated protective responses. Using a rat model of 30 minutes of 70% warm ischemia followed by reperfusion, RNA for microarray analysis was extracted from the non-ischemic and the ischemic-reperfused lobes at four reperfusion times: 0 (no reperfusion), 0.5, 2, and 6 hours. Differentially expressed genes and pathway analyses were used to identify IR-induced events. The transcriptome of the reperfused lobes was unique and discrete at each reperfusion time, showing no evidence of sustained changes of the gene expression alterations seen at 30 minutes of reperfusion. At all reperfusion times, a significant portion of gene expression changes in the reperfused lobes were present in the non-ischemic lobes. However, the earliest reperfusion time, 30 minutes, showed a marked increase in the expression of a set of immediate-early genes (c-Fos, c-Jun, Atf3, Egr1) that was exclusive to the reperfused lobe. Similarities of gene expression changes in the reperfused and the non-ischemic lobes at each time suggest that hemodynamics and/or circulating factors are potent stimuli in an IR model. However, early reperfusion events appear to reflect a cell-autonomous response that may be protective, thereby representing potential targets to ameliorate IR injury.
2019-12-16 | GSE117915 | GEO
Project description:This is an ordinary differential equation model of the early inflammatory response during transplantion. Descriptions are included of the inflammatory events associated with the initial surgical procedure, the subsequent ischemia/reperfusion (I/R) events that cause tissue damage to the host as well as the donor graft, and the inflammatory effects of T cells.
2019-11-19 | MODEL1911190001 | BioModels