Biology subjects

Karampelias, C.

Publications and source records attributed to Karampelias, C..

4 recordsLinked to original sources

bioRxiv2026

Integrated histological and proteomic mapping of pancreatic adaptations during porcine pregnancy

Pregnancy is a period of extensive metabolic rewiring. Insulin secreting {beta}-cells respond to the metabolic challenges of pregnancy by increasing their mass and size and by altering secretory patterns to maintain glucose homeostasis. If glucose metabolism is not tightly controlled, gestational diabetes may develop. Most studies on {beta}-cell adaptation during pregnancy are derived from rodent models, making translation to the vastly different human gestational setting challenging. In this work, we performed an extensive characterization of pancreatic adaptations throughout porcine pregnancy. Pigs have a long gestational period (114 days) and share a similar size and metabolism to humans, making them an ideal model to bridge the knowledge gap between rodents and humans. By analyzing pancreatic samples from early and late gestational ages, we captured the full trajectory of endocrine remodeling. We observed pregnancy-driven remodeling of endocrine cell types, marked by preferential expansion of pancreatic polypeptide-secreting cells. Proteomic characterization of the pancreas from early and late gestation showed a downregulation of SLC20A2 and ZCCHC7, identifying new protein targets involved in physiological endocrine cell adaptation. Overall, our comprehensive characterization of pancreatic adaptations in the pig model helps bridge the translational gap between rodents and humans and highlights previously unrecognized proteins with therapeutic potential for gestational diabetes.

developmental biology↗

bioRxiv2025

Benchmarking porcine pancreatic ductal organoids for drug screening applications

Primary human pancreatic ductal organoids (HPDO) have emerged as a model to study pancreas biology and disease. Yet, donor material availability, and a lack of extensive benchmarking limits the range of applications. To address this gap, we established porcine pancreatic ductal organoids (PPDO) as a system from an easily obtainable source to model pancreatic ductal/progenitor biology. We benchmarked PPDO to HPDO and primary porcine pancreas using single-cell RNA sequencing (scRNA-Seq). We observed no overt phenotypic differences in PPDO derived from distinct developmental stages, with a WNT signaling enriched population characterizing PPDO. PPDO exhibited differentiation potential towards mature ductal cells and limited potential towards endocrine lineages. We used PPDO as a platform to assess the safety of FDA-approved drugs and showed conserved toxicity of statins and -adrenergic receptor inhibitors between PPDO and HPDO cultures. Overall, our results highlight the PPDO as a model for mammalian duct/progenitor applications.

developmental biology↗

bioRxiv2024

Characterization of liver-pancreas crosstalk following beta-cell loss reveals a role for the molybdenum cofactor in beta-cell regeneration

Regeneration of insulin-producing {beta}-cells is an alternative avenue to manage diabetes, and it is crucial to unravel this process in vivo during physiological responses to the lack of {beta}-cells. Here, we aimed to characterize how hepatocytes can contribute to {beta}-cell regeneration in a zebrafish model of {beta}-cell ablation. Using lineage-tracing, we show that hepatocytes do not directly convert into {beta}-cells even under extreme {beta}-cell ablation conditions. A transcriptomics analysis of isolated hepatocytes following {beta}-cell ablation displayed altered lipid- and glucose-related processes. Based on the transcriptomics, we performed a genetic screen that uncovers a potential role for the molybdenum cofactor (Moco) biosynthetic pathway in {beta}-cell regeneration and glucose metabolism in zebrafish. Consistently, Mocs2 haploinsufficiency in mice indicated dysregulated glucose metabolism and liver function. Together, our study sheds light on the liver-pancreas crosstalk and suggests that the molybdenum cofactor biosynthesis pathway should be further studied in relation to glucose metabolism and diabetes.

developmental biology↗

bioRxiv2023

Biodistribution of DNA-origami nanostructures in live zebrafish embryos with single-cell resolution

DNA origami-based nanotechnology is a versatile tool for exploring fundamental biological questions and holds significant promise for future biomedical applications. However, the development of DNA origami-based therapeutic agents is hindered by the challenge of translating in vitro performance into effective applications in vivo. Here, we exploit the optical transparency of the embryonic zebrafish to track intravenously injected, fluorescently labelled wireframe DNA origami nanostructures. Our approach integrated long-term, high-resolution imaging of transgenic live embryos with single-cell RNA sequencing, to elucidate the biodistribution of DNA nanostructures over time, up to 3 days post-injection (dpi). Notably, we observed rapid accumulation of nanostructures in the caudal hematopoietic tissue (CHT), akin to the fetal liver in mammals. We tested the effects of coating the nanostructures with an oligolysine PEG copolymer (K-PEG), a widely used strategy to enhance their stability. The K-PEG coating mitigated the accumulation rate in CHT, enabling higher percentages of the nanostructures to engage with other tissues. Additionally, our findings highlighted the pivotal role of scavenger endothelial cells in DNA origami clearance, with K-PEG offering sustained protection for the nanostructures at the CHT. Furthermore, by monitoring DNA origami in a transgenic zebrafish line designed for targeted macrophage ablation, we found that macrophages contribute to nanostructure clearance at later time points. This study introduces a framework for the analyses of the biodistribution and clearance of DNA origami nanostructures in vivo with single cell resolution and establishes a foundation for the investigation of DNA origami-based nanomedicines in animal models.

bioengineering↗