Department of Pediatrics and Department of Biology, University of Virginia, Charlottesville, Virginia, USA.
Department of Hematology, West German Cancer Center, University Hospital Essen, Essen, Germany.
Sci Rep. 2017 Mar 24;7:45205. doi: 10.1038/srep45205.
The cardiac endothelium plays a crucial role in the development of a functional heart. However, the precise identification of the endocardial precursors and the mechanisms they require for their role in heart morphogenesis are not well understood. Using in vivo and in vitro cell fate tracing concomitant with specific cell ablation and embryonic heart transplantation studies, we identified a unique set of precursors which possess hemogenic functions and express the stem cell leukemia (SCL) gene driven by its 5' enhancer. These hemo-vascular precursors give rise to the endocardium, atrioventricular cushions and coronary vascular endothelium. Furthermore, deletion of the sphingosine-1-phosphate receptor 1 (S1P1) in these precursors leads to ventricular non-compaction cardiomyopathy, a poorly understood condition leading to heart failure and early mortality. Thus, we identified a distinctive population of hemo-vascular precursors which require S1P1 to exert their functions and are essential for cardiac morphogenesis.
心脏内皮在功能性心脏的发育中起着至关重要的作用。然而，确切的心脏内胚层前体细胞的鉴定以及它们在心脏形态发生中所需的机制还不是很清楚。通过体内和体外的细胞命运追踪，以及特定的细胞消融和胚胎心脏移植研究，我们鉴定了一组独特的前体细胞，它们具有造血功能，并表达由其 5'增强子驱动的干细胞白血病（SCL）基因。这些造血血管前体细胞产生心内膜、房室瓣垫和冠状动脉内皮。此外，在这些前体细胞中敲除鞘氨醇-1-磷酸受体 1（S1P1）会导致心室非致密性心肌病，这是一种导致心力衰竭和早期死亡的发病机制尚不清楚的疾病。因此，我们鉴定了一群独特的造血血管前体细胞，它们需要 S1P1 来发挥其功能，对于心脏形态发生是必不可少的。
