Branch Point Smooth Muscle Cells Highlighted by Novel Lineage Tracking Approach.

Abstract

Advances in genetic fate mapping techniques have changed our understanding of the origins and fates of vascular smooth muscle cells (VSMCs) in vivo.1–5 When considered in its entirety, the vascular system is a large and diverse structure with numerous organ-specific variations.6,7 Blood vessel networks are dynamic and adaptive reflecting processes used to build and remodel such networks in the embryo.8 The smooth muscle composition of these networks is mosaic in origin,9,10 yet most of our inducible genetic tools are expressed in all VSMCs and fail to capture VSMC subsets. In this issue of Circulation Research , Roostalu et al11 report a new approach to fate mapping VSMCs that suggests a way forward for lineage tracking VSMC subsets in vivo. In the process, they identify an intriguing subset of immature VSMCs formed in the embryo that is traced to branch points and bifurcations in disease-prone arteries. Article, see p 267 The authors began by searching for genes that uniquely identify the earliest VSMCs that form around the E10.5 dorsal aorta in the mouse embryo. They focused on the expression dynamics of NG2 (neural/glial antigen-2, Cspg4 ) and CD146 (melanoma cell adhesion molecule [ Mcam ]). CD146 is a 113-kDa cell adhesion molecule of the immunoglobulin superfamily and a receptor for the α4 chain of laminin. CD146/ Mcam is highly expressed by endothelial cells, embryonic VSMCs, and mesenchymal stem cells. NG2/ Cspg4 is expressed by embryonic VSMCs, adipocytes, pericytes, and chondrocytes. Therefore, early differentiating VSMCs are uniquely identified by the combined expression of NG2 and CD146. For most aortic VSMCs, this combined expression pattern is transient as CD146 expression is downregulated in the thoracic aorta by E16.5 and in the abdominal aorta around the time of birth. However, VSMCs of smaller caliber …