A new resource for human coronary vessel development.
A new resource for human coronary vessel development.
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DOI：
10.1093/cvr/cvac094
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发表时间：
2022-06
影响因子：
10.8
通讯作者：
Ragini Phansalkar;K. Red-Horse
中科院分区：
文献类型：
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作者：
Ragini Phansalkar;K. Red-Horse
冠状血管和供应心脏的血管在胚胎和出生后发育期间形成。虽然小鼠冠状动脉血管系统的发育已经得到了很好的研究，但更好地了解人类冠状动脉的发育对于促进受损成人心脏的动脉再生至关重要。在这项研究中，麦克拉肯等人1对来自发育中的人类心脏的超过10000个冠状动脉内皮细胞（EC）进行了单细胞RNA测序（scRNAseq）（图1）。尽管先前的研究2 -3已经在人类心脏上进行了scRNAseq，但富集如此大量的EC对于回答有关细胞起源的问题并预测细胞命运轨迹的更深层次的询问至关重要。麦克拉肯等人在妊娠第13周和第14周对人类心脏进行了scRNAseq。小鼠发育的等效阶段（e15和e18之间）以显著的血管生长和重塑而闻名。他们的数据包括各种EC类型，包括毛细血管、动脉、静脉、淋巴管和内皮细胞。他们发现了微血管和大血管动脉群，以及两个由INMT或KIT表达标记的毛细血管细胞群，与先前的研究一致。4重要的是，作者使用SCENIC 5进行基因调控网络分析，以揭示调控人类冠状动脉发育的转录因子（TF）。MECOM是通过该分析确定的动脉调节因子之一，除了先前已知的TF，包括HEY 1和SOX 17。作者使用原位杂交验证了MECOM在人胎儿心脏动脉中的表达。Mecom的表达也发现在小鼠心脏的动脉EC，支持其在动脉发育的重要性。作者进一步验证了其在通过siRNA介导的MECOM敲低从人胚胎干细胞（hESC-EC）分化的动脉EC中实现和/或维持动脉表型中的作用。6在MECOM敲低后，hESC-EC呈现出更多的静脉转录谱，同时保留动脉标记物的表达，表明MECOM参与静脉基因表达的抑制。
The coronary vasculature and the blood vessels supplying the heart are formed during embryonic and post-natal development. While the development of the coronary vasculature in mice has been well-studied, a better understanding of human coronary artery development is essential for efforts to promote arterial regeneration in injured adult hearts. In this study, McCracken et al. 1 performed single-cell RNA sequencing (scRNAseq) of over 10 000 coronary endothelial cells (ECs) from developing human hearts (Figure 1). Although prior studies2–3 have performed scRNAseq on human hearts, the enrichment of such a large number of ECs is critical for deeper interrogations that answer questions about cell origins and predict cell fate trajectories. McCracken et al. conducted scRNAseq on human hearts at gestational weeks 13 and 14. The equivalent stage of mouse development, between e15 and e18, is notable for significant vascular growth and remodelling. Their data comprise a variety of EC types including capillary, artery, vein, lymphatic, and endocardial. They uncovered both micro-and macro-vascular arterial populations, as well as two populations of capillary cells marked by expression of either INMT or KIT, consistent with a previous study. 4Importantly, the authors employed gene regulatory network analysis using SCENIC 5 to uncover transcription factors (TFs) regulating human coronary development. MECOM is one of the arterial regulators identified through this analysis, in addition to previously known TFs including HEY1 and SOX17. The authors validated MECOM expression in the arteries of human fetal hearts using in situ hybridization. Mecom expression was also found in arterial ECs of mouse hearts, supporting its importance in arterial development. The authors further validated its role in achieving and/or maintaining an arterial phenotype with an siRNA-mediated knockdown of MECOM in arterial EC differentiated from human embryonic stem cells (hESC-ECs). 6 After MECOM knockdown, hESC-ECs took on a more venous transcriptional profile while retaining expression of arterial markers, indicating that MECOM is involved in the suppression of venous gene expression.