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Expression of human lungs at cold ischemic time (CIT) and 1-2 hrs. after reperfusion (H)

ABSTRACT: Study on lung transplantation encompassing a comprehensive and detailed investigation of differences at transcription level between lungs before and after transplant.

ORGANISM(S): Homo sapiens

PROVIDER: GSE145989 | GEO | 2023/02/01

REPOSITORIES: GEO

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Expression of human lungs at cold ischemic time (CIT) and 1-2 hrs. after reperfusion (H)

Project description:Expression of human lungs at cold ischemic time (CIT) and 1-2 hrs. after reperfusion (H)

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Mapping Ischemia Reperfusion Inflammatory Responses in Human Lung Transplantation at Single-Cell Resolution

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

Lung transplantation-induced cold ischemia–reperfusion injury in the murine lung

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

Single-cell analysis reveals the immune heterogeneity and interactions in lungs undergoing hepatic ischemia-reperfusion

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

Expression data from donor lungs of cardiac death and brain death donors (re-analysis)

Project description:Ischemia reperfusion induced injury contributes to poor lung transplant outcomes.Microarrays were used to study the biological response of human lungs to the ischemia reperfusion process. Samples were collected from lung transplant cases at Toronto General Hospital. Lungs were donation after brain death (DBD)

2023-09-18 | GSE127242 | GEO

Expression of Human Lung by Donor Type and EVLP Type

Project description:Study on lung transplantation encompassing a comprehensive and detailed investigation of differences at transcription level between DBD and DCD donor lungs.

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Expression data from biopsies of CIT study patients

Project description:We aimed to investigate the effect of increased cold ischemia time (CIT) on gene expression profiles of implantation and clinically indicated biopsies early after transplantation and the impact of basiliximab (BAS) versus rabbit antithymocyte globulin (rATG) induction therapies on clinical outcomes and intragraft molecular features A retrospective, single-centered cohort study was designed to compare the safety and efficacy of rATG versus BAS for induction in patients who received a renal transplantation from a deceased donor between January 2007 and December 2012. Recipients with CIT greater than 20 hours were included in this study. Patients were excluded if they had received a prior transplantation or dual organ transplantation. Patients were followed for 12 months post-transplantation or until patient death, graft lost or lost to follow up. Patients in the rATG group received 1.5 mg per kilogram of body weight given intravenously with the initial dose given intraoperatively. Subsequent doses were given daily through post-operative day 3, for a total dose of 4.5-6.0 mg per kilogram. Dosing was adjusted based on daily white blood cell and platelet counts. BAS (20 mg given intravenously) was administered intraoperatively and the subsequent dose on day 3 post-transplantation. All patients received maintenance immunosuppression with tacrolimus, prednisone and mycophenolate mofetil. In total. 230 patients were transplanted with a CIT > 20 hours; 174 and 56 patients received rATG and BAS induction, respectively. Gene expression profiling ws carried out on a subset (n=28) of these patients' post transplant biopsies. Of those 28 patients, 16 received rATG and 12 received BAS induction treatment.

2015-09-10 | E-GEOD-72355 | biostudies-arrayexpress

B cells mediate lung ischemia-reperfusion injury by recruitment of CCR2+-classical monocytes via synergistic BCR-TLR4 signaling

Project description:Ischemia reperfusion injury (IRI)-mediated primary graft dysfunction (PGD) adversely impacts both short- and long-term outcomes after lung transplantation, a procedure which remains the only treatment option for patients suffering from end-stage respiratory failure. While B cells can regulate adaptive immune responses through antibody production, antigen presentation and secretion of cytokines, their role in lung IRI is not well understood. Here, we demonstrate by intravital imaging that B cells are rapidly recruited to injured lungs, where they extravasate into the parenchyma. Using hilar clamping and transplant models, we observe that lung-infiltrating B cells produce the monocyte chemokine CCL7 in Toll-like receptor 4 (TLR4)-TRIF-dependent fashion, a critical step contributing to classical monocyte (CM) recruitment and subsequent neutrophil extravasation, resulting in worse lung function. We find that synergistic BCR-TLR4 activation on B cells is required for the recruitment of CMs to the injured lung. Finally, we corroborate our findings in reperfused human lungs, where we observe a correlation between B cell infiltration and CM recruitment after transplantation. This study uncovers a role for B cells as critical orchestrators of lung IRI. As B cells can be depleted with currently available agents, our study provides a rationale for clinical trials investigating B cell-targeting therapies.

2024-03-20 | GSE249242 | GEO

Cold Storage Disrupts the Proteome Landscape in Rat Kidney Transplants

Project description:Approximately 70% of kidney grafts are obtained from deceased donors, and these grafts must be preserved in hypothermic conditions to prolong their viability until transplantation. However, prolonged cold storage (CS) of kidneys results in poor long-term outcomes after transplantation. We reported previously that CS of rat kidneys for 18 h prior to transplant impaired proteasome function, disrupted protein homeostasis, and reduced graft function. The goal of the present study was to identify the renal proteins that are dysregulated by this CS-induced injury. Isolated donor Lewis rat kidneys were subject to 18-h CS and transplanted into recipient Lewis rats (CS+Tx). Autotransplantation (ATx: transplant with 0-h CS) or Sham (right nephrectomy) surgeries served as controls. The proteome of kidney homogenates was analyzed with tandem mass-tag mass spectrometry to identify CS-induced abnormalities in kidney grafts. CS injury disrupted the renal phosphoproteome in kidney grafts and dysregulated numerous signaling pathways. Integrated analysis of global proteomes and phosphoproteomes identified 15 proteins that were significantly regulated in a CS-specific manner. In particular, proteins and pathways such as complement and coagulation cascades were upregulated, while antioxidant pathways, such as glutathione, were suppressed in CS+Tx groups compared to ATx and Sham controls. This study, for the first time, provides deeper insight into the disruption of the renal graft proteome caused by CS injury and provides a novel set of pathways and molecules that can be investigated to delineate their specific role in renal transplant outcomes, ultimately improving outcomes for patients with end-stage kidney disease.

2024-04-18 | MSV000094566 | MassIVE

Characterizing Macrophage Diversity in Metastasis-Bearing Lungs Reveals a Lipid-Associated Macrophage Subset

Project description:Single cell RNA sequencing was performed on CD45+Ly6G-CD64+MerTK+ macrophages isolated from the lungs of mice 5 weeks after transplantation of 4T1-Luc mammary gland tumors. The purpose of this study was to determine the unique macrophage subsets present in the lungs of mice bearing mammary tumor metastases.

2021-08-31 | GSE164302 | GEO

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