Unveiling Complexity and Multipotentiality of Early Heart Fields.
Unveiling Complexity and Multipotentiality of Early Heart Fields.
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DOI：
10.1161/circresaha.121.318943
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发表时间：
2021-08-06
影响因子：
20.1
通讯作者：
Chi, Neil C.
中科院分区：
文献类型：
--
作者：
Zhang, Qingquan;Carlin, Daniel;Zhu, Fugui;Cattaneo, Paola;Ideker, Trey;Evans, Sylvia M.;Bloomekatz, Joshua;Chi, Neil C.
胚胎外组织，包括卵黄囊和胎盘，以及胚胎内的心脏，为胚胎提供关键的营养。先天性心脏病（CHD）与胚外组织缺陷的相关性进一步支持了心脏与胚外组织之间潜在的发育关系。虽然早期心脏谱系的发育已经得到了很好的研究，但心脏谱系（包括心外膜）和胚外中胚层之间的发育关系仍有待确定。探讨心脏谱系与胚外谱系的发育关系。通过高分辨率的单细胞和遗传谱系/克隆分析，我们显示了胚外中胚层和心脏谱系之间的未知克隆关系。单细胞转录组学和轨迹分析揭示了两个中胚层祖细胞来源有助于左心室心肌细胞，一个胚胎和其他胚胎外基因表达签名。额外的谱系追踪研究显示，胚外相关祖细胞位于原肠胚中的胚胎-胚外界面，并产生不同的细胞类型，形成心包、横隔、心外膜、左心室和房室管心肌的背外侧区域以及胚外中胚层。克隆分析表明，这些祖细胞是多能性的，不仅产生心肌细胞和serum mesothelium细胞类型，但也显着，胚外中胚层。总的来说，我们的研究结果揭示了以前未知的多能心血管祖细胞在胚胎-胚外界面的位置，并定义了serum mesotherapy谱系的最早胚胎起源，包括心外膜，其为心脏提供成纤维细胞和血管支持细胞。我们的研究揭示了胚胎心血管谱系和胚外中胚层之间的共同谱系关系，强调了胚胎和胚外中胚层之间界限的模糊。我们的研究结果表明，先天性心脏病和胎盘功能不全异常之间的关联意想不到的基础，以及胚胎外细胞用于产生心脏修复的心血管细胞类型的潜在效用。
Extraembryonic tissues, including the yolk sac and placenta, and the heart within the embryo, work to provide crucial nutrients to the embryo. The association of congenital heart defects (CHDs) with extraembryonic tissue defects further supports the potential developmental relationship between the heart and extraembryonic tissues. Although the development of early cardiac lineages has been well-studied, the developmental relationship between cardiac lineages, including epicardium, and extraembryonic mesoderm remains to be defined. To explore the developmental relationships between cardiac and extraembryonic lineages. Through high-resolution single cell and genetic lineage/clonal analyses, we show an unsuspected clonal relationship between extraembryonic mesoderm and cardiac lineages. Single-cell transcriptomics and trajectory analyses uncovered two mesodermal progenitor sources contributing to left ventricle cardiomyocytes, one embryonic and the other with an extraembryonic gene expression signature. Additional lineage-tracing studies revealed that the extraembryonic-related progenitors reside at the embryonic-extraembryonic interface in gastrulating embryos, and produce distinct cell types forming the pericardium, septum transversum, epicardium, dorsolateral regions of the left ventricle and atrioventricular canal myocardium, and extraembryonic mesoderm. Clonal analyses demonstrated that these progenitors are multipotent, giving rise to not only cardiomyocytes and serosal mesothelial cell types but also, remarkably, extraembryonic mesoderm. Overall, our results reveal the location of previously unknown multipotent cardiovascular progenitors at the embryonic-extraembryonic interface, and define the earliest embryonic origins of serosal mesothelial lineages, including the epicardium, which contributes fibroblasts and vascular support cells to the heart. The shared lineage relationship between embryonic cardiovascular lineages and extraembryonic mesoderm revealed by our studies underscores an underappreciated blurring of boundaries between embryonic and extraembryonic mesoderm. Our findings suggest unexpected underpinnings of the association between congenital heart disease and placental insufficiency anomalies, and the potential utility of extraembryonic cells for generating cardiovascular cell types for heart repair.