A model for angiogenesis suppression via SERPINF1 in the surrounding pro-acinar microenvironment during human fetal pancreas development

Abstract

AbstractPancreas hormone-producing endocrine cell islets are integrated with the blood supply, whereas pancreatic digestive-enzyme producing acini are not. The functional result is that pancreatic acinar cells release their digestive enzymes into the ductal system and the duodenum to aid in digestion, while pancreatic hormone-producing endocrine cells release their hormones, such as insulin and glucagon, into the bloodstream. Despite this understanding, the mechanism for how acinar cells are free of vascularization is not completely clear. Based on an analysis of publicly available single cell RNA-sequencing data (GSE110154) of the human fetal pancreas during gestational weeks 12 through 22, a model is proposed that draws upon the anti-angiogenic properties of SERPINF1. This model envisions +PTF1A/+SOX9/+CPA1 pancreatic pro-acinar tip progenitor and +COL1A2/+PDGFRA pancreatic stromal fibroblast cell populations that surround the developing acini secreting SERPINF1 (PEDF) to inhibit angiogenesis and endothelial cell generation. This secretion could maintain an acinar microenvironment that is free from robust vascularization and integration of blood vessels as seen in mature pancreatic islet of Langerhans/endocrine cells.