PDF(Pubmed)
Abstract：
To form fully functional four-chambered structure, mammalian heart development undergoes a transient finger-shaped trabeculae, crucial for efficient contraction and exchange for gas and nutrient. Although its developmental origin and direct relevance to congenital heart disease has been studied extensively, the time-resolved cellular mechanism underlying hypotrabeculation remains elusive. Here, we employed in toto live imaging and reconstructed the holistic cell lineages and cellular behavior landscape of control and hypotrabeculed hearts of mouse embryos from E9.5 for up to 24 h. Compared to control, hypotrabeculation in ErbB2 mutants arose mainly through dual mechanisms: both reduced proliferation of trabecular cardiomyocytes from early cell fate segregation and markedly impaired oriented cell division and migration. Further examination of mosaic mutant hearts confirmed alterations in cellular behaviors in a cell autonomous manner. Thus, our work offers a framework for continuous live imaging and digital cell lineage analysis to better understand subtle pathological alterations in congenital heart disease.
摘要：
为了形成功能齐全的四腔结构，哺乳动物的心脏发育经历了短暂的指状小梁，对于有效收缩和交换气体和营养至关重要。尽管它的发育起源和与先天性心脏病的直接相关性已经得到了广泛的研究，神经根低的时间分辨细胞机制仍然难以捉摸。这里,我们在toto活成像和重建的整体细胞谱系和细胞行为景观的对照和小鼠胚胎的心脏从E9.5长达24小时。与对照相比，ErbB2突变体的小梁形成不足主要是通过双重机制产生的：早期细胞命运分离导致小梁心肌细胞增殖减少，定向细胞分裂和迁移明显受损。对镶嵌突变心脏的进一步检查证实了细胞行为以细胞自主方式的改变。因此，我们的工作为连续实时成像和数字细胞谱系分析提供了框架,以更好地了解先天性心脏病的细微病理改变.
