Uncovering the transcriptomic heterogeneity of pancreatic endothelial cells using integrative and comparative single cell gene expression analysis

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.19.537540v1?rss=1 Authors: Khan, S. T., Ahuja, N., Taib, S., Vohra, S., Cleaver, O., Nunes, S. S. Abstract: The pancreatic islet vasculature displays tissue-specific physiological and functional adaptations that support rapid glucose sensing and insulin response by beta-cells. To uncover the transcriptomic basis of this specialization, we performed a meta-analysis of multi-organ single cell RNA sequencing atlases employing a unique strategy to avoid transcriptomic contamination. We identified biologically relevant genes involved in sphingosine-1-phosphate-mediated insulin secretion (PLPP1, RDX, CDC42), islet basement membrane formation (SPARC, COL15A1), endothelial cell (EC) permeability (PLVAP, EHD4), membrane transporters (CD320, SLCO2A1) and developmental transcription factors (NKX2-3, AHR). These were validated in silico in an independent dataset. We further established the first integrated transcriptomic atlas of human pancreatic ECs and described two unique capillary subpopulations: exocrine and endocrine pancreas ECs. We validated the spatial localization of key markers using RNAscope and immunofluorescence staining on mouse pancreatic tissue cross-sections. Our findings provide novel insights into pancreatic EC heterogeneity and islet EC function with potential implications in therapeutic strategies. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC