Expression data of pig pancreas from Oncopig tumor and normal pigs
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ABSTRACT:
PROVIDER: PRJNA838007 | ENA |
REPOSITORIES: ENA
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Project description:In order to determine the difference in expression between pancreatic tumors generated from OCM or Oncopigs and wild type pig pancreas, we have harvested pancreatic tumors and normal pancreas from two OCM subjects and two normal pigs, respectively.
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Project description:Human pancreas development remains incompletely understood due to limited sample access constrained by ethical and practical considerations. Here we investigate whether pigs resemble humans in pancreas development more closely than rodents, and as such, offer a valuable alternative large-animal model. As pig pancreas organogenesis is unexplored, we first annotated developmental hallmarks and lineage markers of pancreas differentiation and morphogenesis throughout the 114-day gestation. Building on this detailed roadmap, we further constructed a pig single-cell multiome atlas capturing temporal resolution across all three trimesters. Cross-species comparisons with human and mouse time-resolved integrated pancreas atlases accentuated that pig closely resembled human in developmental tempo, epigenetic and transcriptional regulation, gene expression patterns and gene regulatory networks (GRNs). Specifically, pig mimicked the dynamics of progenitor status, differentiation trajectories and GRNs governing endocrine fate acquisition in human. In pig multiome GRN, over 40% of transcription factors targeted by NEUROG3, the endocrine master regulator, were confirmed in human stem cell models. Most notably, we uncovered beta-cell heterogeneity arising during embryonic development, owing to endocrine induction in pancreatic progenitors with temporally altered epigenetic and transcriptional identity. Overall, our work lays the foundation for using pigs to model human pancreas biology and provides unprecedented insights into developmental principles and mechanisms across species.
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Project description:Human pancreas development remains incompletely understood due to limited sample access constrained by ethical and practical considerations. Here we investigate whether pigs resemble humans in pancreas development more closely than rodents, and as such, offer a valuable alternative large-animal model. As pig pancreas organogenesis is unexplored, we first annotated developmental hallmarks and lineage markers of pancreas differentiation and morphogenesis throughout the 114-day gestation. Building on this detailed roadmap, we further constructed a pig single-cell multiome atlas capturing temporal resolution across all three trimesters. Cross-species comparisons with human and mouse time-resolved integrated pancreas atlases accentuated that pig closely resembled human in developmental tempo, epigenetic and transcriptional regulation, gene expression patterns and gene regulatory networks (GRNs). Specifically, pig mimicked the dynamics of progenitor status, differentiation trajectories and GRNs governing endocrine fate acquisition in human. In pig multiome GRN, over 40% of transcription factors targeted by NEUROG3, the endocrine master regulator, were confirmed in human stem cell models. Most notably, we uncovered beta-cell heterogeneity arising during embryonic development, owing to endocrine induction in pancreatic progenitors with temporally altered epigenetic and transcriptional identity. Overall, our work lays the foundation for using pigs to model human pancreas biology and provides unprecedented insights into developmental principles and mechanisms across species.
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Project description:Human pancreas development remains incompletely characterized due to restricted sample access. We investigate whether pigs resemble humans in pancreas development, offering a complementary large-animal model. As pig pancreas organogenesis is unexplored, we first annotate developmental hallmarks throughout its 114-day gestation. Building on this, we construct a pig single-cell multiome pancreas atlas across all trimesters. Cross-species comparisons reveal pig closely resembles human in developmental tempo, epigenetic and transcriptional regulation, and gene regulatory networks. This further extends to progenitor dynamics and endocrine fate acquisition. Transcription factors regulated by NEUROG3, the endocrine master regulator, are over 50% conserved between pig and human, many being validated in human stem cell models. Notably, we uncover that during embryonic development, emerging beta-cell heterogeneity coincides with a species-conserved primed endocrine cell (PEC) population alongside NEUROG3-expressing cells. Overall, our work lays the foundation for comparative investigations and offers unprecedented insights into evolutionary-conserved pancreas organogenesis mechanisms across animal models.
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Project description:Human pancreas development remains incompletely characterized due to restricted sample access. We investigate whether pigs resemble humans in pancreas development, offering a complementary large-animal model. As pig pancreas organogenesis is unexplored, we first annotate developmental hallmarks throughout its 114-day gestation. Building on this, we construct a pig single-cell multiome pancreas atlas across all trimesters. Cross-species comparisons reveal pig closely resembles human in developmental tempo, epigenetic and transcriptional regulation, and gene regulatory networks. This further extends to progenitor dynamics and endocrine fate acquisition. Transcription factors regulated by NEUROG3, the endocrine master regulator, are over 50% conserved between pig and human, many being validated in human stem cell models. Notably, we uncover that during embryonic development, emerging beta-cell heterogeneity coincides with a species-conserved primed endocrine cell (PEC) population alongside NEUROG3-expressing cells. Overall, our work lays the foundation for comparative investigations and offers unprecedented insights into evolutionary-conserved pancreas organogenesis mechanisms across animal models.
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Project description:Acute pancreatitis (AP) is acute inflammation of the pancreas, mainly caused by gallstones and alcohol, driven by changes in communication between cells. Heparin-binding proteins (HBPs) play a central role in cell communication. Therefore, we used heparin affinity proteomics to identify extracellular HBPs in pancreas and plasma of normal mice and in a caerulein mouse model of AP. Many new extracellular HBPs (360) were discovered in the pancreas, taking the total number of HBPs known to 786. Extracellular pancreas HBPs form highly interconnected protein-protein interaction networks in both normal pancreas (NP) and AP. Thus, HBPs represent an important set of extracellular proteins with significant regulatory potential in the pancreas. HBPs in NP are associated with biological functions such as molecular transport and cellular movement that underlie pancreatic homeostasis. However, in AP HBPs are associated with additional processes such as acute phase response signalling, complement activation and mitochondrial dysfunction. Plasma HBPs in AP included known AP biomarkers such as serum amyloid A, as well as emerging targets such as histone H2A. Pancreas HBPs are extracellular and so easily accessible and are potential drug targets in AP, whereas plasma HBPs represent potential biomarkers for AP.
2018-12-17 | PXD012039 | Pride