We acquired scRNA-seq data of over 10 000 foetal cardiac endothelial cells (ECs), revealing divergent EC subtypes including endocardial, capillary, venous, arterial, and lymphatic populations. Gene regulatory network analyses predicted roles for SMAD1 and MECOM in determining the identity of capillary and arterial populations, respectively. Trajectory inference analysis suggested an endocardial contribution to the coronary vasculature and subsequent arterialization of capillary endothelium accompanied by increasing MECOM expression. Comparative analysis of equivalent data from murine cardiac development demonstrated that transcriptional signatures defining endothelial subpopulations are largely conserved between human and mouse. Comprehensive characterization of the transcriptional response to MECOM knockdown in human embryonic stem cell-derived EC (hESC-EC) demonstrated an increase in the expression of non-arterial markers, including those enriched in venous EC.
scRNA-seq of the human foetal cardiac endothelium identified distinct EC populations. A predicted endocardial contribution to the developing coronary vasculature was identified, as well as subsequent arterial specification of capillary EC. Loss of MECOM in hESC-EC increased expression of non-arterial markers, suggesting a role in maintaining arterial EC identity.
我们获得了超过10000个胎儿心脏内皮细胞(EC)的scRNA-seq数据,显示不同的EC亚型,包括心内膜,毛细管,静脉,动脉,和淋巴种群。基因调控网络分析预测SMAD1和MECOM在确定毛细血管和动脉种群身份中的作用,分别。轨迹推断分析表明,心内膜对冠状动脉血管系统的贡献以及随后的毛细血管内皮动脉化伴随着MECOM表达的增加。来自鼠心脏发育的等效数据的比较分析表明,定义内皮亚群的转录特征在人和小鼠之间很大程度上是保守的。人类胚胎干细胞来源的EC(hESC-EC)对MECOM敲低的转录反应的综合表征表明,非动脉标志物的表达增加,包括那些富含静脉EC的。
人胎儿心脏内皮的scRNA-seq鉴定了不同的EC群体。确定了预测的心内膜对发育中的冠状动脉血管的贡献,以及随后的毛细血管EC的动脉规范。在hESC-EC中MECOM的缺失增加了非动脉标志物的表达,提示在维持动脉EC身份中的作用。