Potential Antigens Involved In Delayed Xenograft Rejection in a GGTA1/CMAH DKO Pig-To-Monkey Model
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ABSTRACT:
PROVIDER: PRJNA390077 | ENA |
REPOSITORIES: ENA
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Project description:When hyperacute rejection is avoided by deletion of Gal expression in the pig, delayed xenograft rejection (DXR) becomes a major immunologic barrier to successful xenotransplantation. This study was to investigate potential antigens involved in DXR. We isolated primary renal microvascular endothelial cells (RMEC) and aortic endothelial cells (AEC) from GGTA1/CMAH double-knockout (DKO) pig and immunized monkeys with both of these cells. After sensitization, monkey serum antibody binding and cytotoxicity to RMEC was significantlyhigher than to AEC,suggesting that RMEC are more immunogenic than AEC. Transcriptome sequencing of DKO pigs indicated that the expression of 1,500 genes was higher in RMEC than in AEC, while 896 genes was lower. The differentially-expressed genes were mainly related to cell and biological adhesion.
2019-07-07 | GSE99914 | GEO
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Project description:Embryonic stem cells (ESCs) may be able to cure or alleviate the symptoms of various degenerative diseases. However, unresolved issues regarding apoptosis, maintaining function and tumor formation mean a prudent approach should be taken towards advancing ESCs into human clinical trials. The rhesus monkey provides the ideal model organism for developing strategies to prevent immune rejection and test the feasibility, safety and efficacy of ESC-based medical treatments. Transcriptional profiling of rhesus ESCs provides a foundation for future pre-clinical ESC research using non-human primates as the model organism. In this research we use microarray, immunocytochemistry, real-time and standard RT-PCR to characterize and transcriptionally profile rhesus monkey embryonic stem cells. We identify 367 rhesus monkey stemness genes, we demonstrate the high level (>85%) of conservation of rhesus monkey stemness gene expression across five different rhesus monkey embryonic stem cell lines, we demonstrate that rhesus monkey ESC lines maintain a pluripotent undifferentiated state over a wide range of Pou5f1 (Oct-4) expression levels and we compare rhesus monkey, human and murine stemness genes to identify the key mammalian stemness genes. The supplementary tables list the genes that have been upregulated in each undifferentiated rhesus monkey embryonic stem cell line (GSM99998, GSM99999,GSM100000, GSM100001, GSM100002, GSM99965, GSM99966) in comparison analysis with the pooled differentiated embryonic stem cells (GSM99840). Supplemental Table 1 contains the comparison analysis for all 52,865 probe sets on the rhesus monkey gene chip, Supplemental Table 2 contains the rhesus monkey genes that were significantly upregulated (FC>3) in the ORMES-6 biological replicates, Supplemental Table 3 contains the rhesus monkey genes that were significantly upregulated (FC>3) in the pooled differentiated EBs and Supplemental Tables 4-8 represent genes that were significantly upregulated in ORMES 6A, 7, 9, 10 and 13 respectively. Supplemental Table 9 contains the RT-PCR primers used in this project. Keywords: Rhesus monkey embryonic stem cell microarray
2006-08-17 | GSE4446 | GEO
Project description:Cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) and Programmed death-1 (PD-1) are immunoregulatory receptors expressed on T cells that play important roles in suppressing immune responses to cancer. Although monoclonal antibodies that target CTLA-4 or PD-1 stimulate therapeutic anti-tumour T cell responses, the tumour antigens recognized by checkpoint blockade immunotherapy remain undefined. Herein, we use genomics and bioinformatics approaches to identify tumour-specific mutant proteins as a major class of T cell rejection antigens following αPD-1 and/or αCTLA-4 treatment of mice bearing progressively growing sarcomas. We validate this conclusion by showing that (a) the predicted mutant epitopes associate with MHC class I molecules of the tumour; (b) T cells specific for these mutant epitopes infiltrate tumours; and (c) therapeutic vaccines incorporating these mutant epitopes induce tumour rejection comparably to checkpoint blockade immunotherapy. Whereas, T cells with the same antigen specificity are present in progressively growing tumours in control mice, tumour-specific T cells in αPD-1- and/or αCTLA-4-treated mice express some overlapping but mostly treatment-specific transcriptional profiles that render them capable of tumour rejection. Thus, tumour-specific mutant antigens are not only important targets of checkpoint blockade therapy but also can be used to identify tumour antigen-specific T cells that function as biomarkers of successful anti-tumour responses.
2014-11-07 | GSE62771 | GEO
Project description:Acute renal allograft rejection is an important complication in kidney transplantation. Accurate diagnosis of rejection events is necessary for timely response and treatment. We illustrate the usefulness and biological relevance of selected multivariate approaches to detect rejection from genomic and proteomic signals. The data was used to study gene expression changes using whole genome microarray analysis of peripheral blood from subjects with acute rejection (n=20) and non-rejecting controls (n=20) to obtain insight into the molecular and biological causation of acute renal allograft rejection when combined with proteomics (iTRAQ) data for the same patients/time-points.
2014-04-26 | GSE46474 | GEO
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Project description:Previous studies of rejection-associated transcript expression in heart transplant biopsies identified not only rejection but a group of early biopsies with injury but no rejection. The present analysis used an expanded population of biopsies to explore parenchymal injury in all biopsies, with or without rejection, and its relationship to function, and outcome. Archetypal analysis defined five injury clusters: no-injury (N=376); mild (N=526); moderate (N=110); severe (N=87); and late (N=221). The late group, 62% of which had no rejection, had molecular characteristics associated with atrophy-fibrosis, depressed LVEF, and increased graft loss independent of rejection status. In random forest analysis, low LVEF was more strongly associated with injury scores than with rejection scores. Three-year graft failure was best predicted using a combination of injury and rejection scores. In heart transplant biopsies, injury-related molecular scores correlate with dysfunction and risk of failure and identify an important new group of late heart transplants, many with no rejection, that have impaired function and a high risk of graft loss. (ClinicalTrials.gov #NCT02670408).
2021-12-28 | GSE150059 | GEO
Project description:Rhesus Monkey is one of the important primate models widely used in the fields of disease mechanism study, pre-clinical test in drug discovery and molecular evolution. However, the majority of rhesus gene annotations were putatively mapped from human genome, with only 10% supported by rhesus EST data.So, to better study the transcriptome, paired-end, strand-specific, poly(A)-positive RNA-Seq were performed in 5 rhesus monkey tissues. 5 tissue samples examined: prefrontal cortex, liver, skeletal muscle, adipose, testis
2012-10-10 | E-GEOD-34426 | biostudies-arrayexpress
Project description:PINK1 protein is highly expressed in primate brains. CRISPR-Cas9-mediated depletion of PINK1in fetal and adult monkey brains causes severe neurodegeneration without affecting mitochondrial proteins and morphology.
2022-02-16 | PXD023520 | Pride