Vasculogenic Pericytes Directly Couple to the Emerging Endothelium During Vessel Formation

Abstract

Vascular pericytes (PCs) stabilize blood vessels and contribute to their maturation, while also playing key roles in microvascular function. Nevertheless, relatively little is known about their involvement in the earliest stages of vascular development, specifically during vasculogenesis. We combined high-power, time-lapse imaging with transcriptional profiling of PCs and endothelial cells (ECs) in reporter mouse and cell lines. PCs emerged alongside EC differentiation, and physically engaged the vasculogenic endothelium in vivo and in vitro. We observed PC-EC coupling and identified Connexin43 (Cx43)-based gap junctions as key elements in PC-EC communication during vessel assembly. We found no overlap between differentiating PCs and other lineages including hemangiogenic and neuronal/glial cell types. Together, our data suggest that a distinct PC lineage emerges prior to vasculogenesis and participates in early vessel formation through direct communication with nascent endothelium via Cx43 – providing insight that reshapes the current framework of vascular development and informs tissue vascularization strategies.