Aix Marseille Univ, INSERM, Marseille Medical Genetics, Marseille, France.
Aix Marseille Univ, CNRS UMR7288, IBDM, Marseille, France.
Elife. 2020 Aug 17;9:e55124. doi: 10.7554/eLife.55124.
Perturbation of addition of second heart field (SHF) cardiac progenitor cells to the poles of the heart tube results in congenital heart defects (CHD). The transcriptional programs and upstream regulatory events operating in different subpopulations of the SHF remain unclear. Here, we profile the transcriptome and chromatin accessibility of anterior and posterior SHF sub-populations at genome-wide levels and demonstrate that Hoxb1 negatively regulates differentiation in the posterior SHF. Spatial mis-expression of in the anterior SHF results in hypoplastic right ventricle. Activation of in embryonic stem cells arrests cardiac differentiation, whereas -deficient mouse embryos display premature cardiac differentiation. Moreover, ectopic differentiation in the posterior SHF of embryos lacking both and its paralog results in atrioventricular septal defects. Our results show that Hoxb1 plays a key role in patterning cardiac progenitor cells that contribute to both cardiac poles and provide new insights into the pathogenesis of CHD.
第二心脏场（SHF）心脏祖细胞添加到心脏管极的干扰导致先天性心脏缺陷（CHD）。在 SHF 的不同亚群中起作用的转录程序和上游调节事件尚不清楚。在这里，我们在全基因组水平上对前 SHF 和后 SHF 亚群的转录组和染色质可及性进行了分析，并证明 Hoxb1 负调控后 SHF 中的分化。在前 SHF 中的空间异位表达导致右心室发育不良。在胚胎干细胞中激活会阻止心脏分化，而 -缺陷的小鼠胚胎则显示出过早的心脏分化。此外，在缺乏 及其同源物 的胚胎的后 SHF 中异位分化导致房室间隔缺损。我们的研究结果表明，Hoxb1 在心脏祖细胞的模式形成中起着关键作用，这些祖细胞有助于心脏的两极，并为 CHD 的发病机制提供了新的见解。
