Single-nucleus Transcriptomics Reveals Cardiac Cell Type-specific Diversification in Metabolic Disease Transgenic Pigs
Ontology highlight
ABSTRACT:
ORGANISM(S): Sus scrofa
PROVIDER: GSE245458 | GEO | 2024/04/30
REPOSITORIES: GEO
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Project description:Single-nucleus Transcriptomics Reveals Cardiac Cell Type-specific Diversification in Metabolic Disease Transgenic Pigs
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Project description:Intrauterine exposure to disturbed maternal glucose metabolism is associated with adverse consequences for the offspring. Hepatic disorders in affected offspring emerge in early development; thus, detection of disease biomarkers at an early stage may elucidate the underlying mechanisms of maternal hyperglycemia-induced metabolic disease and improve timely diagnosis and treatment strategies. To systematically study the molecular consequences of maternal hyperglycemia, we used data independent acquisition (DIA) proteomics and compared the molecular profiles of liver of three days old wild-type piglets born to a transgenic hyperglycemic pig model with those of wild-type piglets born to normoglycemic mothers.
2023-07-10 | PXD040305 | Pride
Project description:Purpose: ME/CFS is a lifelong debilitating disease that affects approximately 1% of the global population. Previous studies have identified dysfunctional activity in metabolic, immune and neurological pathways. The goal of this study is to identify ME/CFS specific variations in DNA methylation to determine whether the patient specific epigenetic patterns provide insight into the disease pathophysiology. Methods: DNA was extracted from the PBMCs of 10 ME/CFS patients and age/gender matched controls. After performing RRBS the sequence was aligned to hg19 genome using Bismark. The data was analyzed using first an ANOVA F test through DMAP in order to determine variation between the patient and control groups across 40-220bp fragments of the genome. Additional analysis was performed following a MethylKit pipeline, which analyzed the variation on a single CpG basis using a Fishers test. Results: From a total of 146,575 DMAP fragments we identified 76 differentially methylated fragments (P <0.05, Diff meth +/- 15%). A total of 31 were associated with gene regions (intronic/exonic). MethylKit analysis also identified a total of 394 differentially methylated cytosines (FDR corrected P <0.05, Diff meth +/- 15%) from a total of 196,172 individual analyzed cytosines, 91 of the statistically significant cytosines fell within gene regions. Comparison of both methylomes and regions where both the DMAP fragments and multiple MethylKit cytosines fell highlighted areas of the genome containing regulatory elements associated with metabolic and immune activity. Gene body pathway enrichment additionally identified immune metabolic and neurological related functions. Conclusions: Our study represents the first investigation of ME/CFS patients using reduced representation bisulfite sequencing. We identified a number of major differences between patients that distinguished them from healthy controls. Our results identified a number of differentially methylated regulatory elements and gene bodies that highlight the disturbed pathophysiology in ME/CFS. In particular the large number of enriched neurotransmitter and neuropeptide reactome pathways highlighted a disturbed neurological pathophysiology in patients.
2020-07-02 | GSE153667 | GEO
Project description:Gene expression profiles from pig jejunum scrapings either fed or fasted at four and six weeks of age (n=16 per group). Result indicate that the fasting intervention was more severe in the four-week-old piglets, but also induced changes functinal changes in especially metabolic function and cell proliferation in the six-week-old piglets.
2024-02-28 | GSE203439 | GEO
Project description:INSC94Y transgenic pigs serve as a valuable model for permanent neonatal diabetes mellitus. Through genetically engineered modifications in the insulin (INS) gene, this model presents with impaired insulin secretion, resulting elevated fasting blood-glucose levels (hyperglycemia) [1].One of the severe complications of diabetes mellitus are hypoglycemia-mediated morphological abnormalities in the retina, also described as diabetic retinopathy (DR). Adjacent to the retina lies the vitreous, a gelatinous, highly hydrated matrix, which is important for ocular function and retinal physiology. It contains variety of proteins and signaling molecules, which are useful for the characterization of the biological activity of the vitreous itself, and may help to elucidate molecular processes occurring in the retina, especially under pathophysiological conditions and in disease. To gain insight into the proteomic profile of porcine vitreous and detect possible differences relevant to DR pathogenesis, we used discovery proteomics for analysis of INSC94Y vitreous compared to wild-type controls. Reference: [1] Renner, S.; Braun-Reichhart, C.; Blutke, A.; Herbach, N.; Emrich, D.; Streckel, E.; Wunsch, A.; Kessler, B.; Kurome, M.; Bahr, A.; et al. Permanent neonatal diabetes in INS(C94Y) transgenic pigs. Diabetes 2013, 62, 1505-1511, doi:10.2337/db12-1065.
2024-08-27 | PXD038198 | Pride
Project description:Comprehensive transcriptomic survey of the pig (Sus scrofa) may lead to a better understanding of mechanisms of tissue specialization that underlie economic traits of this species and accelerate its use as a biomedical model. Here, we characterized four distinct transcript types (lncRNAs, TUCPs, miRNAs and circRNAs) in 31 adult pig tissues and two cell lines, together with protein-coding genes. We dissected their distinct structural and transcriptional features and uncovered transcriptome variability as related to tissue physiology. We discovered extraordinary diversity among 47 anatomically distinct skeletal muscle types, as well as among six adipose depots, which are linked to their diverse origins, metabolic features, cell composition, physical activity and mitochondrial pathways. In particular, transcription of HOX genes across skeletal muscles exhibited a position-dominant pattern, revealing a similar developmental history of these tissues within the same body part. Transcriptional patterns across adipose depots demonstrated a metabolically protective role of subcutaneous adipose tissue and the association of visceral adipose tissue with metabolic dysfunction. Comparative analysis of the transcriptomes of seven tissues of the pig and nine other vertebrates revealed insights into evolutionary divergence of transcription that contributes to lineage-specific tissue biology. We also analyzed long-range regulation of promoters by their enhancers with downstream transcription in subcutaneous adipose tissues of six mammals, showing that evolutionary stability of transcription can mainly be attributed to multiple enhancers buffering gene expression patterns against genetic perturbations, thereby conferring robustness during speciation. Collectively, this study offers a resource for the accelerated use of the pig as a biomedical model for human biology and disease and uncovers molecular bases of its diverse economic traits.
2021-04-20 | GSE161882 | GEO
Project description:Comprehensive transcriptomic survey of the pig (Sus scrofa) may lead to a better understanding of mechanisms of tissue specialization that underlie economic traits of this species and accelerate its use as a biomedical model. Here, we characterized four distinct transcript types (lncRNAs, TUCPs, miRNAs and circRNAs) in 31 adult pig tissues and two cell lines, together with protein-coding genes. We dissected their distinct structural and transcriptional features and uncovered transcriptome variability as related to tissue physiology. We discovered extraordinary diversity among 47 anatomically distinct skeletal muscle types, as well as among six adipose depots, which are linked to their diverse origins, metabolic features, cell composition, physical activity and mitochondrial pathways. In particular, transcription of HOX genes across skeletal muscles exhibited a position-dominant pattern, revealing a similar developmental history of these tissues within the same body part. Transcriptional patterns across adipose depots demonstrated a metabolically protective role of subcutaneous adipose tissue and the association of visceral adipose tissue with metabolic dysfunction. Comparative analysis of the transcriptomes of seven tissues of the pig and nine other vertebrates revealed insights into evolutionary divergence of transcription that contributes to lineage-specific tissue biology. We also analyzed long-range regulation of promoters by their enhancers with downstream transcription in subcutaneous adipose tissues of six mammals, showing that evolutionary stability of transcription can mainly be attributed to multiple enhancers buffering gene expression patterns against genetic perturbations, thereby conferring robustness during speciation. Collectively, this study offers a resource for the accelerated use of the pig as a biomedical model for human biology and disease and uncovers molecular bases of its diverse economic traits.
2021-04-20 | GSE162146 | GEO
Project description:Comprehensive transcriptomic survey of the pig (Sus scrofa) may lead to a better understanding of mechanisms of tissue specialization that underlie economic traits of this species and accelerate its use as a biomedical model. Here, we characterized four distinct transcript types (lncRNAs, TUCPs, miRNAs and circRNAs) in 31 adult pig tissues and two cell lines, together with protein-coding genes. We dissected their distinct structural and transcriptional features and uncovered transcriptome variability as related to tissue physiology. We discovered extraordinary diversity among 47 anatomically distinct skeletal muscle types, as well as among six adipose depots, which are linked to their diverse origins, metabolic features, cell composition, physical activity and mitochondrial pathways. In particular, transcription of HOX genes across skeletal muscles exhibited a position-dominant pattern, revealing a similar developmental history of these tissues within the same body part. Transcriptional patterns across adipose depots demonstrated a metabolically protective role of subcutaneous adipose tissue and the association of visceral adipose tissue with metabolic dysfunction. Comparative analysis of the transcriptomes of seven tissues of the pig and nine other vertebrates revealed insights into evolutionary divergence of transcription that contributes to lineage-specific tissue biology. We also analyzed long-range regulation of promoters by their enhancers with downstream transcription in subcutaneous adipose tissues of six mammals, showing that evolutionary stability of transcription can mainly be attributed to multiple enhancers buffering gene expression patterns against genetic perturbations, thereby conferring robustness during speciation. Collectively, this study offers a resource for the accelerated use of the pig as a biomedical model for human biology and disease and uncovers molecular bases of its diverse economic traits.
2021-04-20 | GSE162145 | GEO
Project description:Comprehensive transcriptomic survey of the pig (Sus scrofa) may lead to a better understanding of mechanisms of tissue specialization that underlie economic traits of this species and accelerate its use as a biomedical model. Here, we characterized four distinct transcript types (lncRNAs, TUCPs, miRNAs and circRNAs) in 31 adult pig tissues and two cell lines, together with protein-coding genes. We dissected their distinct structural and transcriptional features and uncovered transcriptome variability as related to tissue physiology. We discovered extraordinary diversity among 47 anatomically distinct skeletal muscle types, as well as among six adipose depots, which are linked to their diverse origins, metabolic features, cell composition, physical activity and mitochondrial pathways. In particular, transcription of HOX genes across skeletal muscles exhibited a position-dominant pattern, revealing a similar developmental history of these tissues within the same body part. Transcriptional patterns across adipose depots demonstrated a metabolically protective role of subcutaneous adipose tissue and the association of visceral adipose tissue with metabolic dysfunction. Comparative analysis of the transcriptomes of seven tissues of the pig and nine other vertebrates revealed insights into evolutionary divergence of transcription that contributes to lineage-specific tissue biology. We also analyzed long-range regulation of promoters by their enhancers with downstream transcription in subcutaneous adipose tissues of six mammals, showing that evolutionary stability of transcription can mainly be attributed to multiple enhancers buffering gene expression patterns against genetic perturbations, thereby conferring robustness during speciation. Collectively, this study offers a resource for the accelerated use of the pig as a biomedical model for human biology and disease and uncovers molecular bases of its diverse economic traits.
2021-04-20 | GSE162143 | GEO