State Key Laboratory of Pharmaceutical Biotechnology, Department of Cardiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing 210061, China.
State Key Laboratory of Pharmaceutical Biotechnology, Department of Cardiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing 210061, China.
Dev Biol. 2019 Jun 15;450(2):82-89. doi: 10.1016/j.ydbio.2019.03.019. Epub 2019 Apr 2.
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.
在小鼠的发育过程中，部分来源于第二心脏场（SHF）祖细胞的细胞有助于流出道（OFT）的伸长和扩大，随后 OFT 分隔成主动脉（Ao）和肺动脉（PA）的干。因此，心脏祖细胞起源的细胞分布在 Ao 和 PA 中。在这里，我们通过谱系追踪技术研究了这些细胞在 OFT 分隔过程中是如何分配到两个大动脉的。通过使用诱导型 Mef2c-AHF-CreERT2；Rosa26-mTmG 报告系统，鉴定了两个 SHF 祖细胞波及其衍生物，它们分别对 Ao 和 PA 做出了不同的贡献。而早期的细胞波（在 E7.5）优先定向 Ao，第二个细胞波（从 E8.5 到 E11.5）则更喜欢通向 PA。此外，我们发现 PDK1 是第二波细胞的关键调节因子，因为 Pdk1 的缺失导致发育不良的 PA 导致肺动脉狭窄。因此，这项研究深入了解了心脏祖细胞衍生的细胞的预定细胞命运，它们优先贡献 Ao 和 PA，以及肺动脉狭窄的发病机制。
