Differential contribution of the two waves of cardiac progenitors and their derivatives to aorta and pulmonary artery.

During mouse development, part of the cells derived from the second heart field (SHF) progenitors contributes to the elongation and enlargement of the outflow tract (OFT) that subsequently septates into the trunks of aorta (Ao) and pulmonary artery (PA). Thus, the cardiac progenitor-originated cells are distributed to both Ao and PA. Here, we investigated that how these cells are assigned to the two great arteries during OFT septation through lineage tracing technology. By use of the inducible Mef2c-AHF-CreERT2; Rosa26-mTmG reporter system, two waves of SHF progenitors and their derivatives were identified, and they made differential contribution to the Ao and PA, respectively. While the early wave of cells (at E7.5) was preferentially destined to the Ao, the second wave of cells (from E8.5 till E11.5) made its favorite path to the PA. In addition, we unveiled PDK1 as a critical regulator of the second wave of cells as deletion of Pdk1 resulted in poorly developed PA leading to pulmonary stenosis. Thus, this study provides insights into the understanding of the pre-determined cell fate of the cardiac progenitor-derived cells with preferential contribution to the Ao and PA, as well as of the pathogenesis of pulmonary stenosis.