PDF(Pubmed)
Abstract：
Coronary vasculature formation is a critical event during cardiac development, essential for heart function throughout perinatal and adult life. However, current understanding of coronary vascular development has largely been derived from transgenic mouse models. The aim of this study was to characterize the transcriptome of the human foetal cardiac endothelium using single-cell RNA sequencing (scRNA-seq) to provide critical new insights into the cellular heterogeneity and transcriptional dynamics that underpin endothelial specification within the vasculature of the developing heart.
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.
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.
摘要：
冠状动脉血管形成是心脏发育过程中的关键事件，在整个围产期和成年期对心脏功能至关重要。然而,目前对冠状动脉血管发育的认识主要来自转基因小鼠模型.这项研究的目的是使用单细胞RNA测序（scRNA-seq）表征人类胎儿心脏内皮的转录组，以提供对细胞异质性和转录动力学的重要新见解，从而支撑内皮细胞在发育中的血管内的规格心脏。
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。
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。
