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Spatial transcriptomic analysis reveals increased adipogenesis and non-alcoholic fatty liver disease pathway in pig-to-NHP islet transplantation recipient liver during early post-transplantation period

ABSTRACT: Spatial transcriptomic analysis reveals increased adipogenesis and non-alcoholic fatty liver disease pathway in pig-to-NHP islet transplantation recipient liver during early post-transplantation period

PROVIDER: PRJNA1087728 | ENA |

REPOSITORIES: ENA

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Spatial transcriptomic analysis reveals increased adipogenesis and non-alcoholic fatty liver disease pathway in pig-to-NHP islet transplantation recipient liver during early post-transplantation period

Project description:Pancreatic islet transplantation stands out as a promising therapeutic avenue for type 1 diabetes patients grappling with glycemic instability and hypoglycemia unawareness. Given the persistent scarcity of donor organs, there is growing anticipation that pig-to-human islet xenotransplantation will emerge as the definitive beta cell replacement therapy for this condition. The liver is the site of preclinical pig-to-NHP islet transplantation as well as allogeneic clinical transplantation, yet there’s still a lack of understanding on the pathology of the liver after the transplantation procedure. Based on our observations of post-transplantation periportal pathologic changes in primate models, we have conducted a retrospective study examining the hepatic pathology in pig-to-NHP islet recipients with short-term graft survival, employing a state-of-the-art spatial transcriptomic platform within the vicinity of the islet implantation site. Post-transplantation liver tissue could be easily distinguished into three regions based on transcriptional profiles, consistent with its histology. A notable elevation in adipogenesis and non-alcoholic fatty liver disease (NAFLD) pathways could be identified, which included increased expression of SREBF1, CEBPA, IGF1, and TNFRSF12A. We furthermore discovered that, despite the decreased severity of the multifocal white lesions indicated by gross examination at 33 days post-transplantation, there was still evidence of NAFLD at the transcriptional level. These results prompt further research into the relationship between intrahepatic islet transplantation and hepatic microenvironment.

2025-05-31 | GSE261581 | GEO

murine primary basal cell (BC) recipient (69 days post-transplantation) and ESC-derived basal cell (iBC) recipient (192 days post-transplantation)

Project description:The goal of the experiment is to: 1) compare transcriptome of primary BC-derived lineages to endogenous tracheal epithelial cells after transplantation; 2) compare the transcriptome of iBC-derived lineages to their endogenous counterparts, and study them together with a previous dataset of iBC recipient 40&56 days post-transplantation to study any temporal changes

2023-08-24 | GSE211996 | GEO

NK CELL TOLERANCE IN LIVER TRANSPLANTATION IS RELATED TO STAT4 DOWNREGULATION

Project description:Liver transplantation (LT) is a definitive treatment for end-stage liver disease and hepatocellular cancer. As donor-recipient HLA matching is not employed, there is potential for natural killer (NK) cell-mediated alloreactivity. Here we report that recipient NK cells exhibit a downregulated phenotype with reduced expression of activating receptors NKp30 and NKp46. We found associated hypofunctionality, with impaired NK cell cytotoxicity, degranulation and IFN-gamma production. Gene expression analysis using microarray and quantitative PCR identified significant downregulation of STAT-4 in LT with associated reduction in miR-155, a microRNA target of STAT-4 and a key regulator of NK differentiation. These data indicate that LT induces recipient NK cell tolerance through altered peripheral maturation at a step prior to the acquisition of inhibitory receptors for HLA class I.

2014-02-01 | E-MTAB-2132 | biostudies-arrayexpress

Liver Transplantation for Non-Resectable Colorectal Liver Metastasis

Project description:The study aims to evaluate the efficacy of liver transplantation in the context of non-resectable colorectal liver metastasis. The primary endpoint is the overall survival in this group of patients while the secondary endpoint is the disease-free survival. Patients included in this protocol will be evaluated either for whole or partial liver transplantation from deceased or living donors. Type of different transplantations proposed are as follows: 1. Whole liver graft or partial liver (split) from a deceased donor 2. Partial liver graft retrieved from a deceased donor and orthotopically implanted after having performed a left hepatectomy in the recipient. 3. Partial liver graft retrieved from a deceased donor and heterotopically implanted if total hepatectomy can not be performed. 4. Partial liver graft retrieved from a living donor and orthotopically implanted after having performed total hepatectomy. 5. Partial liver graft retrieved from a living donor and orthotopically implanted after having after having performed a left hepatectomy in the recipient. 6. Partial liver graft retrieved from a living donor and heterotopically implanted if total hepatectomy can not be performed. In cases 2-3-5-6 total hepatectomy of native liver can be secondarily performed after having achieved a proper graft hypertrophy in order to avoid a small for size syndrome

| 2400483 | ecrin-mdr-crc

murine primary basal cell (BC) recipient (69 days post-transplantation) and ESC-derived basal cell (iBC) recipient (192 days post-transplantation)

Project description:murine primary basal cell (BC) recipient (69 days post-transplantation) and ESC-derived basal cell (iBC) recipient (192 days post-transplantation)

| PRJNA873120 | ENA

RNA-seq data of liver samples in FMT recipient rats

Project description:DHEA-shaped gut microbiota was transplantated to pseudo germ- free rats. Glucose intolerance, liver lipid accumulation and dyslipidemia were observed in recipient rats. Therefore, liver gene expression of these recipient rats were investigated.

2021-05-19 | GSE151220 | GEO

Living Donor Liver Transplantation With Two Stage Hepatectomy for Patients With Isolated, Irresectable Colorectal Liver Metastases

Project description:Nearly one third of patients with colorectal cancer develop liver metastases. It is well known that the achievement of a R0-situation is one of the most important factors for a positive long-term outcome. Despite further advantages in multimodal treatment concepts, only 20 - 30 % of the patients with metastases can be resected in curative intention. Recent studies, especially from Norway, have shown that liver transplantation might be a feasible option in well selected patients since the complete hepatectomy with subsequent liver transplantation can be an option for the achievement of a R0 situation. In this study, we pursue the strategy of two-stage hepatectomy combined with a left-lateral living donor liver transplantation. Inclusion criteria are as follows: non-resectable liver metastases of a primary colorectal carcinoma with an assumed portal-venous drainage of the tumor and at least a "stable disease" after a period of eight weeks systemic chemotherapy. Patients are excluded from the study if there is an extrahepatic tumor burden (with the exception of resectable lung metastases) or if the patient is not suitable for liver transplantation due to co-morbidities. The transplantation itself will be undertaken as a living donor liver transplantation where the left lateral liver lobe (liver segments 2 & 3) from a healthy volunteer donor will serve as graft. Prior transplantation, a left hemihepatectomy in the recipient is performed and the left lateral graft will be transplanted in this position. At the end of the transplantation procedure, the right portal vein will be closed to induce a rapid growth of the graft. The second step, and therefore the completion of the operation is performed after a growth period of the transplanted left-lateral lobe: in this procedure, the right hemi-liver of the recipient will be removed and the patient is supposed to be free of tumor at this point in time.

| 2270149 | ecrin-mdr-crc

Gene expression profile in human orthotopic liver transplantation

Project description:We have studied the genes activated in human liver transplantation to identify potential target genes for the prevention or treatment of related injuries. In a first protocol, in order to evaluate the effect of Ischemia-Reperfusion Injury (IRI) on gene expression profile, we compared gene expression levels in transplanted-reperfused livers versus basal values in donor livers, identifying 795 genes significantly modified in human liver after transplantation. Some genes are likely to be completely activated by IRI, as they are not expressed at all in basal livers. In a second protocol, in order to identify gene dysregulations already present in donor livers, which might affect gene expression profile after transplantation, gene expression evaluated in the first study was compared to control livers (espression data retrieved from ArrayExpress database). About 900 genes in donor livers are dysregulated if compared to the control condition. At least 400 of them remain dysregulated or become more and more dysregulated after transplantation. For the first protocol, two biopsies were collected from each liver: 1 biopsy before explantation from the donor, immediately after opening, before ice was applied, and 1 biopsy about 2-3 hours after liver reperfusion in the recipient organism. Gene expression of 5 transplanted livers was compared to that of 5 donor livers. In the second protocol gene expression both of transplanted and donor livers was compared to gene expression data from 5 control livers retrieved from ArrayExpress repository SAMPLE ID: E-AFMX-11. This dataset is part of the TransQST collection.

2009-10-01 | E-GEOD-14951 | biostudies-arrayexpress

Rate of recipient-derived alveolar macrophages development and major histocompatibility complex cross-dressing after lung transplantation in humans

Project description:Analyzing the kenetics of alveolar macrophage turnover after human lung transplantation and identifying protein and transcriptional differences between donor and recipient-derived alveolar macrophages

2021-05-10 | GSE174126 | GEO

Liver tissues of 12h after brain death donor liver transplantation and matched non-brain death donor liver transplantation.

Project description:To determine the circRNA expression profile in hepar tissues of 12h after brain death donor liver transplantation and matched non-brain death donor liver transplantation, we uesed circRNA microArray analysis form Arraystar to examine the expression of circRNAs and circRNAs in hepar tissues of 12h after brain death donor liver transplantation and matched non-brain death donor liver transplantation.

2020-04-10 | GSE119748 | GEO

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