Abstract
In experimental studies, pancreatic islet microvasculature is essential for islet endocrine function and mass, and islet vascular morphology is altered in diabetic subjects. Even so, almost no information is available concerning human islet microvascular endothelial cell (MVEC) physiology and gene expression. In this study, islets and exocrine pancreatic tissue were acquired from organ donors with normoglycemia or impaired glucose metabolism (IGM) immediately after islet isolation. Following single-cell dissociation, primary islet- and exocrine MVECs were obtained through fluorescence-activated cell sorting (FACS) and transcriptional profiles were generated using AmpliSeq. Multiple gene sets involved in general vascular development and extracellular matrix remodeling were enriched in islet MVEC. In exocrine MVEC samples, multiple enriched gene sets that relate to biosynthesis and biomolecule catabolism were found. No statistically significant enrichment was found in gene sets related to autophagy or endoplasmic reticulum (ER) stress. Although ample differences were found between islet- and exocrine tissue endothelial cells, no differences could be observed between normoglycemic donors and donors with IGM at gene or gene set level. Our data is consistent with active angiogenesis and vascular remodeling in human islets and support the notion of ongoing endocrine pancreas tissue repair and regeneration even in the adult human.
Highlights
In experimental studies, pancreatic islet microvasculature is essential for islet endocrine function and mass, and islet vascular morphology is altered in diabetic subjects
Endothelial genes PECAM and VWF were almost exclusively detected in sorted microvascular endothelial cell (MVEC) samples
The most notable findings pertain to the identification of transcriptional differences between islet and exocrine MVECs
Summary
Pancreatic islet microvasculature is essential for islet endocrine function and mass, and islet vascular morphology is altered in diabetic subjects. Using > 32,000 endothelial cell single cell RNA-seq sets from 11 different murine tissues, Kalucka et al constructed a murine endothelial cell transcriptome atlas containing 78 endothelial cell subclusters. They found that endothelial cells in mice differ between and within tissues and kinds of vascular beds, and that endothelial cell subsets in multiple tissues express markers associated with angiogenesis[2]. In human organ donors without diabetes, islet microvascular vessels have a larger diameter and lower density than the exocrine microvasculature[13]. study[16] found a general proliferation in all pancreatic cell types in organ donors with an increased duration of stay in the intensive care unit, suggesting that a general proliferation can be triggered in the human pancreas through hitherto unknown processes
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