Zhou Zhengfang, Wang Jingying, Guo Chaoshe, Chang Weiting, Zhuang Jian, Zhu Ping, Li Xue
Departments of Urology and Surgery, Boston Children's Hospital and Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA; Department of Cardiac Surgery, Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510100, China.
Departments of Urology and Surgery, Boston Children's Hospital and Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
Cell Rep. 2017 Jan 24;18(4):1019-1032. doi: 10.1016/j.celrep.2017.01.002.
The embryonic process of forming a complex structure such as the heart remains poorly understood. Here, we show that Six2 marks a dynamic subset of second heart field progenitors. Six2-positive (Six2) progenitors are rapidly recruited and assigned, and their descendants are allocated successively to regions of the heart from the right ventricle (RV) to the pulmonary trunk. Global ablation of Six2 progenitors resulted in RV hypoplasia and pulmonary atresia. An early stage-specific ablation of a small subset of Six2 progenitors did not cause any apparent structural defect at birth but rather resulted in adult-onset cardiac hypertrophy and dysfunction. Furthermore, Six2 expression depends in part on Shh signaling, and Shh deletion resulted in severe deficiency of Six2 progenitors. Collectively, these findings unveil the chronological features of cardiogenesis, in which the mammalian heart is built sequentially by temporally distinct populations of cardiac progenitors, and provide insights into late-onset congenital heart disease.
诸如心脏这样的复杂结构的胚胎形成过程仍未被充分理解。在此，我们表明Six2标记了第二心脏场祖细胞的一个动态亚群。Six2阳性（Six2）祖细胞被快速招募并分配，其后代依次被分配到从右心室（RV）到肺动脉干的心脏区域。Six2祖细胞的整体消融导致右心室发育不全和肺动脉闭锁。对一小部分Six2祖细胞进行早期阶段特异性消融在出生时并未引起任何明显的结构缺陷，而是导致成年期心脏肥大和功能障碍。此外，Six2的表达部分依赖于Shh信号传导，Shh缺失导致Six2祖细胞严重缺乏。总体而言，这些发现揭示了心脏发生的时间特征，即哺乳动物心脏由不同时间的心脏祖细胞群体依次构建而成，并为迟发性先天性心脏病提供了见解。
