Mapping Ischemia Reperfusion Inflammatory Responses in Human Lung Transplantation at Single-Cell Resolution
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE220797 | GEO | 2024/10/12
REPOSITORIES: GEO
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Project description:Hepatic ischemia-reperfusion IR (HIR) is an unavoidable pathophysiological process during liver transplantation, resulting in systematic sterile inflammation and remote organ injury. Acute lung injury (ALI) is a serious complication after liver transplantation with high postoperative morbidity and mortality. However, the underlying mechanism is still unclear. To assess the phenotype and plasticity of various cell types in the lung tissue microenvironment after HIR at the single-cell level, single-cell RNA sequencing (scRNA-seq) was performed using the lungs from HIR-induced mice.
2024-06-30 | GSE235367 | GEO
Project description:Lung ischemia–reperfusion (IR) injury increases the mortality and morbidity of patients undergoing lung transplantation. The objective of this study was to determine the key initiator of lung IR injury and to evaluate pharmacological therapeutic approaches using a functional inhibitor against the identified molecule. In a mouse hilar clamp model, the combination of RNA sequencing revealed that neutrophils-derived S100A8/A9 plays a central role in inflammatory reactions in lung IR injury.
2022-11-24 | GSE203238 | GEO
Project description:During heart transplantation, storage in cold preservation solution is thought to protect the organ by slowing metabolism; by providing osmotic support; and by minimising ischaemia-reperfusion (IR) injury upon transplantation into the recipient. Despite its widespread use, our understanding of the metabolic changes prevented by cold storage and how warm ischaemia leads to damage is surprisingly poor. Here, we compared the metabolic changes during warm ischaemia (WI) and cold ischaemia (CI) in hearts from mouse, pig, and human. We identified common metabolic alterations during WI and those affected by CI, thereby elucidating mechanisms underlying the benefits of CI, and how WI causes damage. Succinate accumulation is a major feature within ischaemic hearts across species, and CI slows succinate generation, thereby reducing tissue damage upon reperfusion caused by the production of mitochondrial reactive oxygen species (ROS). Importantly, the inevitable periods of WI during organ procurement led to the accumulation of damaging levels of succinate during transplantation, despite cooling organs as rapidly as possible. This damage was ameliorated by metabolic inhibitors that prevented succinate accumulation and oxidation. Our findings suggest how WI and CI contribute to transplant outcome and indicate new therapies for improving the quality of transplanted organs.
2019-09-20 | MTBLS1085 | MetaboLights
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 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:Lung ischemia-reperfusion (IR) is known to occur after lung transplantation or cardiac bypass. IR leads to tissue inflammation and damage, is also associated with increased morbidity and mortality. Various receptors are known to partake in activation of innate immune system, but the downstream mechanism of tissue damage and inflammation is yet unknown. MicroRNAs (miRNA) are in the forefront in regulating ischemia reperfusion injury and are involved in inflammatory response. Here, we have identified by high throughput approach and evaluated distinct set of miRNAs that may play a role in response to IR in rat lung tissue. Top three differentially expressed miRNAs were validated through quantitative PCRs in the IR rat lung model and an in vitro model of IR of hypoxia and reoxygenation exposed type II alveolar cells. Among the miRNAs, miR-18a-5p showed consistent downregulation in both the model systems on IR. Cellular and molecular analysis brought to light a crucial role of this miRNA in ischemia reperfusion. MiR-18a-5p plays a role in IR mediated apoptosis, ROS production and regulates the expression of neuropeptide Galanin. It also influences the nuclear localization of transcription factor: Nuclear factor-erythroid 2 related factor (Nrf2) which in turn may regulate the expression of miR-18a gene. Thus, we have not only established a rat model for lung IR and enumerate the important miRNAs involved in IR but have also extensively characterized the role of miR-18a-5p in the same. This study will have important clinical and therapeutic implications for and during transplantation procedures.
2020-11-19 | GSE161520 | GEO
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: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 (I/R) injury is an unavoidable event occurring during heart transplantation, leading to graft failures and lower long-term survival rate of the recipient. IR causes apoptosis / death of cardiomyocytes, resulting from up-regulation of apoptotic genes and down-regulation of anti-apoptotic genes. We used microarrays to detail the global programme of gene expression underlying cellularisation and identified distinct classes of up-regulated genes during this process. We used microarrays to detect gene expression profile of ischemia reperfusion injured hearts and identified distinct classes of up-regulated and down regulated genes during this I/R.
2013-09-17 | E-GEOD-50884 | biostudies-arrayexpress
Project description:Ischemia reperfusion (I/R) injury is an unavoidable event occurring during heart transplantation, leading to graft failures and lower long-term survival rate of the recipient. microRNAs are major regulators of genes. IR causes apoptosis/death of cardiomyocytes, resulting from up-regulation of apoptotic genes and down-regulation of anti-apoptotic genes which are regulated by microRNA. We used microarrays to detail the global programme of gene expression underlying cellularisation and identified distinct classes of up-regulated genes during this process. We perserved donor hearts with university of Wisconsin solution for 18h at 4C degree before being implanted into recipients to create ischemia reperfusion injury. The preserved hearts were implanted into a syngeneic recipient mice. 24h after transplantation, heart grafts were harvested for microRNA extraction.
2013-09-17 | E-GEOD-50885 | biostudies-arrayexpress