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Specification and Differentiation of Coronary Smooth Muscle
Author(s) -
Majesky Mark,
Dong Xiu Rong,
Maguire Colin,
Rodgers Laurel
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.62.4
Subject(s) - progenitor cell , microbiology and biotechnology , adventitia , biology , notch signaling pathway , sonic hedgehog , mesenchymal stem cell , population , stem cell , cellular differentiation , signal transduction , anatomy , medicine , genetics , environmental health , gene
Lineage mapping studies have shown that progenitors for coronary smooth muscle enter the heart following epithelial to mesenchymal transition (EMT) of epicardial cells. Primary explant culture experiments show that loss of epicardial cell‐cell adhesion is a prerequisite for transcriptional activation of coronary smooth muscle cell (CoSMC) differentiation marker genes. Thus a majority of epicardial cells are specified for a CoSMC fate, but do not express that fate while resident within the intact epicardium. Our studies suggest that epicardial cell‐cell contacts activate Notch‐dependent pathways that oppose receptor tyrosine kinase (PDGFBB, FGF2)‐mediated signals for EMT and thereby maintain the CoSMC progenitor phenotype in the intact epicardium. Later steps in coronary development produce three distinct layers of artery wall. The outer layer is known as the adventitia and is composed of epicardium‐derived cells. We observed that formation of adventitia is accompanied by local activation of sonic hedgehog (Shh) signaling that is restricted to the adventitial layer. Moreover, we found a population of stem cell antigen 1‐positive cells (AdvSca1) resident within this novel domain of Shh signaling with intrinsic potential to differentiate to pericytes and CoSMCs. The role of AdvSca1 progenitors in coronary artery maturation, remodeling and disease will be discussed. Support: HL19242, HL93594.