Gene expression profiles from heart, lung and liver samples of total body irradiated minipigs
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ABSTRACT:
ORGANISM(S): Sus scrofa
PROVIDER: GSE173425 | GEO | 2021/04/27
REPOSITORIES: GEO
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Project description:Gottingen minipigs mirror the physiological radiation response observed in humans and hence make an ideal candidate model for studying radiation biodosimetry for both limited-sized and mass casualty incidents. We examined the whole blood gene expression profiles at day 1, 3 and 7 after total-body irradiation with 1.7, 1.9, 2.1 and 2.3 Gy doses of gamma-rays. Blood taken one day prior to radiation served as control. Six animals per dose group were used The minipigs were monitored for up to 45 days or time to euthanasia necessitated by radiation effects. Survival correlative signatures were identified from the data.
2022-04-25 | GSE173427 | GEO
Project description:Description Primary membranous nephropathy (MN) is an autoimmune kidney disease histomorphologically defined by subepithelial deposition of immune complexes in the glomeruli, and exhibits a high risk for end-stage kidney disease. Circulating antibodies against phospholipase A2 receptor 1 (PLA2R1) are detected in 70-80% of MN patients and correlate with treatment response and prognosis. Experimental proof that human PLA2R1-antibodies induce MN is still missing. Methods: In passive transfer experiments, minipigs received plasma or purified IgG from patients with PLA2R1-associated MN or from healthy controls. PLA2R1-antibodies and proteinuria were monitored using Western blot, ELISA and Coomassie staining. Kidney tissues were analyzed using immunohistochemistry, immunofluorescence, electron microscopy and proteomic analyses. Results: We show that minipigs, like humans, express PLA2R1 on podocytes. Human PLA2R1-antibodies bound to minipig PLA2R1 in-vitro and in-vivo. Passive transfer of human PLA2R1-antibodies, derived from patients with PLA2R1- associated MN, led to the development of histomorphologic characteristics of human early-stage MN in minipigs, activation of components of the complement cascade and induction of low levels of proteinuria. In the later phases of disease, development of an autologous phase of disease was observed. Conclusions: Applying a translational approach from humans to minipigs we show that human PLA2R1-antibodies are pathogenic, although in the heterologous phase of disease only low level proteinuria developed. Proteomic samples: Porcine glomeruli were isolated following previously published protocols known for human glomeruli, with slight modifications (Stahl et al., Kidney Int. 1984;26(1):30–34.). A total of six samples of sieved glomeruli from porcine kidney were used. 1. untreated_negative_control Experiment 1 (passive transfer of human PLA2R1 antibody from PLA2R1-antibody positive patient into minipigs) 2. exp_1_passive_antibody_rep1 Same experimental procedure in two animals (replicate 1) (treated with patient antibody) 3. exp_1_passive_antibody_rep2 Same experimental procedure in two animals (replicate 2) (treated with patient antibody) 4. exp_1_passive_antibody_control control animal for Pig A and B (treated with healthy antibody) Experiment 2 (passive transfer of human plasma from PLA2R1-antibody positive patient into minipigs) 5. exp_2_passive_plasma treated animal (treated with patient plasma) 6. exp_2_passive_plasma_control control animal (treated with healthy plasma)
2022-12-21 | PXD039024 | Pride
Project description:Minipigs have favorable biological characteristics for juvenile toxicity studies to assess efficacy and safety of pediatric drug products. To evaluate at the molecular level the expression of drug targets, drug metabolism pathways or general maturation of organ transcriptomes in minipigs, we used Customized Agilent Micoarrays (Design-ID 050244) for genome-wide gene expression profiling on 9 different tissues from male and female juvenile Göttingen minipigs aged 1 week to 24 months. The gene expression results analyzed in this study are further described in Heckel T. et al. (2015) Functional analysis and transcriptional output of the Göttingen minipig genome. under submission
2015-12-16 | GSE71441 | GEO
Project description:Minipigs resemble many features of human anatomy, physiology, and biochemistry and represent an animal model for drug efficacy and safety testing. To evaluate at the molecular level the expression of drug targets, drug metabolism pathways or general features of organ transcriptomes in minipigs, we used Customized NimbleGen Microarrays (Design-ID: 120229_MiniPig_TH_expr_HX12) for genome-wide gene expression profiling on 18 different tissues from 6 male and 6 female Göttingen minipigs. The gene expression results analyzed in this study are further described in Heckel T. et al. (2015) Functional analysis and transcriptional output of the Göttingen minipig genome. under submission
2015-12-16 | GSE71438 | GEO
Project description:Comprehensive gene expression analysis in BM-resident stromal cells was performed for an overview of BM environmental change caused by total body irradiation (TBI). Total RNA samples collected from BM-resident stromal cells with or without TBI were subjected to high sensitivity DNA microarray assays Three-condition experiment: Unirradiated, 1 day after TBI and 3 days after TBI. Bone marrow stromal cells were obtained from C57BL/6 mice (n = 6) either non-irradiated or after 9.5 Gy irradiation at indicated times.
2016-09-01 | E-GEOD-72235 | biostudies-arrayexpress
Project description:Minipigs have favorable biological characteristics for juvenile toxicity studies to assess efficacy and safety of pediatric drug products. To evaluate at the molecular level the expression of drug targets, drug metabolism pathways or general maturation of organ transcriptomes in minipigs, we used Customized Agilent Micoarrays (Design-ID 050244) for genome-wide gene expression profiling on 9 different tissues from male and female juvenile Göttingen minipigs aged 1 week to 24 months. The gene expression results analyzed in this study are further described in Heckel T. et al. (2015) Functional analysis and transcriptional output of the Göttingen minipig genome. under submission Data of 72 different tissue samples from 9 tissues (cerebral cortex, hypothalamus, cerebellum, liver, kidney, spleen, bone marrow, testis, ovary) and 4 age groups in female (1 week, 4 weeks, 2 months, 4 months) and 5 age groups in male (1 week, 4 weeks, 2 months, 4 months, 2 years) Goettingen minipigs (Ellegaard) were measured. One tissue was measured in 8 technical replicates. The combination of data of female and male pigs could be seen as a kind of biological replicate for most genes.
2015-12-16 | E-GEOD-71441 | biostudies-arrayexpress
Project description:There is a need to identify biomarkers of radiation exposure for use in development of circulating biodosimeters for radiation exposure and for clinical use as markers of radiation injury. Most research approaches for biomarker discovery rely on a single animal model. The current study sought to take advantage of a novel aptamer-based proteomic assay which has been validated for use in many species to characterize changes to the blood proteome after total-body irradiation (TBI) across four different mammalian species including humans. Plasma was collected from C57BL6 mice, Sinclair minipigs, and Rhesus non-human primates (NHPs) receiving a single dose of TBI at a range of 3.3 Gy to 4.22 Gy at 24 h postirradiation. NHP and minipig models were irradiated using a 60Co source at a dose rate of 0.6 Gy/min, the C57BL6 mouse model using an X-ray source at a dose rate of 2.28 Gy/min and clinical samples from a photon source at 10 cGy/min. Plasma was collected from human patients receiving a single dose of 2 Gy TBI collected 6 h postirradiation. Plasma was screened using the aptamer-based SomaLogic SomaScan® proteomic assay technology to evaluate changes in the expression of 1,310 protein analytes. Confirmatory analysis of protein expression of biomarker HIST1H1C, was completed using plasma from C57BL6 mice receiving a 2, 3.5 or 8 Gy TBI collected at days 1, 3, and 7 postirradiation by singleplex ELISA. Summary of key pathways with altered expression after radiation exposure across all four mammalian species was determined using Ingenuity Pathway Analysis (IPA). Detectable values were obtained for all 1,310 proteins in all samples included in the SomaScan assay. A subset panel of protein biomarkers which demonstrated significant (p < 0.05) changes in expression of at least 1.3-fold after radiation exposure were characterized for each species. IPA of significantly altered proteins yielded a variety of top disease and biofunction pathways across species with the organismal injury and abnormalities pathway held in common for all four species. The HIST1H1C protein was shown to be radiation responsive within the human, NHP and murine species within the SomaScan dataset and was shown to demonstrate dose dependent upregulation at 2, 3.5 and 8 Gy at 24 h postirradiation in a separate murine cohort by ELISA. The SomaScan proteomics platform is a useful screening tool to evaluate changes in biomarker expression across multiple mammalian species. In our study, we were able to identify a novel biomarker of radiation exposure, HIST1H1C, and characterize panels of radiation responsive proteins and functional proteomic pathways altered by radiation exposure across murine, minipig, NHP and human species. Our study demonstrates the efficacy of using a multispecies approach for biomarker discovery.
2024-01-03 | GSE252430 | GEO
Project description:Background: Non-human primates, such as Rhesus macaques, are a powerful model for studies of the cellular and physiological effects of radiation, development of radiation biodosimetry, and for understanding the impact of radiation on human health. Here, we study the effects of 4 Gy total body irradiation (TBI) at the molecular level out to 28 days and at the cytogenetic level out to 56 days after exposure. We combine the global transcriptomic and proteomic responses in peripheral whole blood to assess the impact of acute TBI exposure at extended times post irradiation. Results: The overall mRNA response in the first week reflects a strong inflammatory reaction, infection response with neutrophil and platelet activation. At 1 week, cell cycle arrest and re-entry processes were enriched among mRNA changes, oncogene-induced senescence and MAPK signaling among the proteome changes. Influenza life cycle and infection pathways initiate earlier in mRNA and are reflected among the proteomic changes during the first week. Transcription factor proteins SRC, TGF and NFATC2 were immediately induced at 1 day after irradiation with increased transcriptional activity as predicted by mRNA changes persisting up to 1 week. Cell counts revealed a mild / moderate hematopoietic acute radiation syndrome (H-ARS) reaction to irradiation with expected lymphopenia, neutropenia and thrombocytopenia that resolved within 30 days. Measurements of micronuclei per binucleated cell levels in cytokinesis-blocked T-lymphocytes remained high in the range 0.27-0.33 up to 28 days and declined to 0.1 by day 56. Conclusions: Overall, we show that the TBI 4 Gy dose in NHPs induces many cellular changes that persist up to 1 month after exposure, consistent with damage, death, and repopulation of blood cells.
2023-05-10 | PXD037807 | Pride
Project description:Minipigs resemble many features of human anatomy, physiology, and biochemistry and represent an animal model for drug efficacy and safety testing. To evaluate at the molecular level the expression of drug targets, drug metabolism pathways or general features of organ transcriptomes in minipigs, we used Customized NimbleGen Microarrays (Design-ID: 120229_MiniPig_TH_expr_HX12) for genome-wide gene expression profiling on 18 different tissues from 6 male and 6 female Göttingen minipigs. The gene expression results analyzed in this study are further described in Heckel T. et al. (2015) Functional analysis and transcriptional output of the Göttingen minipig genome. under submission A NimbleGen customized 12x135K Gene Expression Array [design ID: 120229_MiniPig_TH_expr_HX12] study using total RNA recovered from drug-naive minipig tissues. Each microarray measures the expression level of 24,499 probe sets covering 17,261 genes with five 60-mer probes (PM) per probe set. The number of replicates is 1 - i.e., only one set of probes on the array. The design includes 16,642 random GC probes for the estimation of the signal threshold and 1536 ERCC control probes.
2015-12-16 | E-GEOD-71438 | biostudies-arrayexpress
Project description:Intervention1: Radiation in prone position using Belly Board device: Comercially available device used to treat patients in prone position who are undergoing external beam pelvic radiation.Patients lie prone on the device during treatment.External beam radiation of 40-45 Gy in 1.8-2 Gy per fraction,one fraction daily,5 days a week, for 4-5 week duration.
Control Intervention1: Radiation in supine position: External beam radiation in supine position.External beam radiation of 40-45 Gy in 1.8-2 Gy per fraction,one fraction daily,5 days a week,for 4-5 week duration.
| 2574599 | ecrin-mdr-crc