Pericytes in Vascular Development

Abstract

Purpose of review: Pericytes are essential components of capillaries in many tissues and organs, contributing to vessel stability and integrity, with additional contributions to microvascular function still being discovered. We review current and foundational studies identifying pericyte differentiation mechanics and their roles in the earliest stages of vessel formation.

Recent findings: Recent advances in pericyte-focused tools and models have illuminated critical aspects of pericyte biology including their roles in vascular development.Pericytes likely collaborate with endothelial cells undergoing vasculogenesis, initiating direct interactions during sprouting and intussusceptive angiogenesis. Pericytes also provide important regulation of vascular growth including mechanisms underlying vessel pruning, rarefaction, and subsequent regrowth.

Keywords: angiogenesis; endothelial cell; mural cell differentiation; pericyte; vascular development; vasculogenesis.

Figure 1.

Schematic illustrating a simplified progression for blood vessel development from vascular cell differentiation to vasculogenesis, subsequent angiogenic remodeling, and lastly vessel maturation and homeostasis. During the early stages of vascular formation, primitive mesoderm (dark green) and pericyte precursors (red) arise from pluripotent embryonic stem cells (yellow). Endothelial cells (green) emerge from mesodermal angioblasts and begin constructing basic vascular structures during vasculogenesis, perhaps with the involvement of mural cells including pericytes. These primitive blood vessels undergo angiogenic remodeling, recruiting pericytes to actively growing vessel networks. A subset of pericytes may further differentiate (red to orange) to contribute to arteriolar vascular smooth muscle cells (orange), as vessel maturation nears completion, and the microvasculature reaches quiescence and homeostasis.

Figure 2.

Confocal image of sprouting endothelial cells labeled for platelet-endothelial cell adhesion molecule-1 (PECAM-1: A and green in D, indicated by light green arrows) with associated pericytes labeled for platelet-derived growth factor receptor-β (PDGFRβ: B and red in D, indicated by pink arrows) in a postnatal day 1 (P1) mouse brain. Cell nuclei are labeled with DAPI (C, and blue in D). All of the denoted pericytes appear to be positioned along emerging endothelial “tip” cells from the base of the filopodia, along the sprout, to the parent vessel. Scale bar in D, 50 μm.