Abstract 20267: Bipotency of Late Cardiac Progenitors; a Possible Role of the Plasticity of Isl1/SLN Atrial Progenitors in Boundary Formation in Cardiac Inflow Tract via Myocardin-dependent Pathway
The cardiac chambers and great vessels form smooth transition at the arterial and venous pole of the heart tube and establish a functional syncytium to facilitate the dynamism of circulatory system. In vitro experiments suggest that multipotent Isl1+ heart progenitors play a pivotal role in lineage diversification, giving rise to both cardiac and smooth muscle cells. A critical question pinpoints when this cardiac-vascular lineage decision is made, how this bipotency serves to coordinate the morphogenesis of cardiac chamber and great vessels, and determining to what extent these steps are irreversible. Here, utilizing atrial-specific sarcolipin (SLN)-Cre knock-in mouse line, we report the discovery of Isl1+/SLN+ atrial progenitors, a subset of Isl1+ second heart field progenitors, their cardiac-smooth muscle bipotency, and its myocardin-dependent mechanism. (1) Newly generated atrial-specific Sarcolipoin (SLN)-Cre knockin mice enabled us to identify Isl1/SLN atrial progenitors, the late subset of cardiac progenitors that are already committed to the atrial lineage but still maintain significant plasticity, in the cardiac inflow tract at E10.5-13.5. (2) Isl1/SLN atrial progenitors showed cardiac-smooth muscle bipotency on cardiac mesenchymal feeder layer. (3) The muscular wall of the cardiac inflow tract consists of two layers - the inner smooth muscle layer and the outer myocardial sleeve - and the atrial progenitors contributed to both cardiac and smooth muscle cells in vivo based on the lineage tracing analysis. (4) Myocardin is a key regulator of the smooth muscle differentiation. Overexpression of Myocardin in the atrial progenitors enhanced smooth muscle differentiation in vitro. (5) Myocardin-null ES cells show little contribution to the smooth muscle layer in the cardiac inflow tract (null ES 73.3+−28.9% vs hetero ES 8.7+−2.9%) but preferential contribution to the atrial myocardium in ES aggregation chimera analysis, suggesting the requirement of Myocardin in the smooth muscle differentiation of the atrial progenitors. These data indicate that the bipotency of the late cardiac progenitors is regulated by Myocardin, and suggest a possible role of the cardiac progenitor plasticity during cardiovascular morphogenesis.
- © 2010 by American Heart Association, Inc.