Differential contribution of the two waves of cardiac progenitors and their derivatives to aorta and pulmonary artery
Differential contribution of the two waves of cardiac progenitors and their derivatives to aorta and pulmonary artery
复制标题
心脏祖细胞及其衍生物的两种波对主动脉和肺动脉的差异贡献
DOI：
10.1016/j.ydbio.2019.03.019
复制
发表时间：
2019
影响因子：
2.7
通讯作者：
Yang Zhongzhou
中科院分区：
文献类型：
--
作者：
Jin Hengwei;Wang Huijuan;Li Jie;Yu Shan;Xu Mingjie;Qiu Zhiqian;Xia Meng;Zhu Jingai;Feng Qiuting;Xie Jun;Xu Biao;Yang Zhongzhou
在小鼠发育过程中，第二心野（SHF）祖细胞的部分细胞参与了流出道（OFT）的伸长和扩大，并随后分化成主动脉（Ao）和肺动脉（PA）的主干。因此，心脏祖细胞来源的细胞分布到Ao和PA两者。在此，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。利用可诱导的Mef 2c-AHF-CreERT 2; Rosa 26-mTmG报告系统，鉴定出两波SHF祖细胞及其衍生物，它们分别对Ao和PA有不同的贡献。虽然早期细胞波（E7.5）优先前往Ao，但第二波细胞（从E8.5到E11.5）最喜欢走PA。此外，我们揭示了PDK 1作为第二波细胞的关键调节因子，因为Pdk 1的缺失导致PA发育不良，导致肺动脉狭窄。因此，这项研究提供了深入了解的预先确定的细胞命运的心脏祖细胞衍生的细胞与优先贡献的Ao和PA，以及肺动脉狭窄的发病机制。
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 inducibleMef2c-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 ofPdk1resulted 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.