title: Pericytes are progenitors for coronary artery smooth muscle.
abstract: 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.
authors.affiliation: Stem Cell and Regenerative Medicine PhD Program, Stanford School of Medicine, Stanford, United States.|Department of Biological Sciences, Stanford University, Stanford, United States.|Institute for Stem Cell and Regenerative Medicine, Stanford School of Medicine, Ludwig Center, Stanford, United States.
authors.forename: Katharina S
authors.initials: KS
authors.lastname: Volz
authors.affiliation: Department of Biological Sciences, Stanford University, Stanford, United States.
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Jacobs
authors.affiliation: Department of Biological Sciences, Stanford University, Stanford, United States.
authors.forename: Heidi I
authors.initials: HI
authors.lastname: Chen
authors.affiliation: Department of Biological Sciences, Stanford University, Stanford, United States.
authors.forename: Aruna
authors.initials: A
authors.lastname: Poduri
authors.affiliation: Department of Biological Sciences, Stanford University, Stanford, United States.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: McKay
authors.affiliation: Department of Biochemistry, Stanford School of Medicine, Stanford, United States.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Riordan
authors.affiliation: Columbia University Medical Center, New York, United States.
authors.forename: Natalie
authors.initials: N
authors.lastname: Kofler
authors.affiliation: Columbia University Medical Center, New York, United States.
authors.forename: Jan
authors.initials: J
authors.lastname: Kitajewski
authors.affiliation: Institute for Stem Cell and Regenerative Medicine, Stanford School of Medicine, Ludwig Center, Stanford, United States.|Ludwig Center for Cancer Stem Cell Biology and Medicine at Stanford University, Stanford, United States.
authors.forename: Irving
authors.initials: I
authors.lastname: Weissman
authors.affiliation: Department of Biological Sciences, Stanford University, Stanford, United States.
authors.forename: Kristy
authors.initials: K
authors.lastname: Red-Horse
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D003331:Coronary Vessels / Q000166:cytology*; D008810:Mice, Inbred C57BL; D032342:Muscle Cells / Q000502:physiology*; D009130:Muscle, Smooth / Q000166:cytology*; D020286:Pericytes / Q000502:physiology*; D000071656:Receptor, Notch3; D051880:Receptors, Notch / Q000096:biosynthesis; D013234:Stem Cells / Q000502:physiology*; D015854:Up-Regulation
chemical_list: C499373:Notch3 protein, mouse; D000071656:Receptor, Notch3; D051880:Receptors, Notch
keywords: Notch signaling; cardiovascular development; developmental biology; mouse; stem cells; vascular smooth muscle