| Autor: |
Volz KS; 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., Jacobs AH; Department of Biological Sciences, Stanford University, Stanford, United States., Chen HI; Department of Biological Sciences, Stanford University, Stanford, United States., Poduri A; Department of Biological Sciences, Stanford University, Stanford, United States., McKay AS; Department of Biological Sciences, Stanford University, Stanford, United States., Riordan DP; Department of Biochemistry, Stanford School of Medicine, Stanford, United States., Kofler N; Columbia University Medical Center, New York, United States., Kitajewski J; Columbia University Medical Center, New York, United States., Weissman I; 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., Red-Horse K; Department of Biological Sciences, Stanford University, Stanford, United States. |
| Abstrakt: |
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. |
