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Pericytes are progenitors for coronary artery smooth muscle

2015; eLife Sciences Publications Ltd; Volume: 4; Linguagem: Inglês

10.7554/elife.10036

2050-084X

Katharina S. Volz, Andrew H Jacobs, Heidi I. Chen, Aruna Poduri, Andrew McKay, Daniel P. Riordan, Natalie Kofler, Jan Kitajewski, Irving L. Weissman, Kristy Red-Horse,

Wnt/β-catenin signaling in development and cancer

Epicardial cells on the heart's surface give rise to coronary artery smooth muscle cells (caSMCs) located deep in the myocardium. However, the differentiation steps between epicardial cells and caSMCs are unknown as are the final maturation signals at coronary arteries. Here, we use clonal analysis and lineage tracing to show that caSMCs derive from pericytes, mural cells associated with microvessels, and that these cells are present in adults. During development following the onset of blood flow, pericytes at arterial remodeling sites upregulate Notch3 while endothelial cells express Jagged-1. Deletion of Notch3 disrupts caSMC differentiation. Our data support a model wherein epicardial-derived pericytes populate the entire coronary microvasculature, but differentiate into caSMCs at arterial remodeling zones in response to Notch signaling. Our data are the first demonstration that pericytes are progenitors for smooth muscle, and their presence in adult hearts reveals a new potential cell type for targeting during cardiovascular disease.