Imagine Institut Pasteur, Laboratory of Heart Morphogenesis, Paris, France.
INSERM UMR1163, Université Paris Descartes, Paris, France.
Nat Rev Cardiol. 2018 Nov;15(11):705-724. doi: 10.1038/s41569-018-0086-9.
The function of the mammalian heart depends on the interplay between different cardiac cell types. The deployment of these cells, with precise spatiotemporal regulation, is also important during development to establish the heart structure. In this Review, we discuss the diverse origins of cardiac cell types and the lineage relationships between cells of a given type that contribute to different parts of the heart. The emerging lineage tree shows the progression of cell fate diversification, with patterning cues preceding cell type segregation, as well as points of convergence, with overlapping lineages contributing to a given tissue. Several cell lineage markers have been identified. However, caution is required with genetic-tracing experiments in comparison with clonal analyses. Genetic studies on cell populations provided insights into the mechanisms for lineage decisions. In the past 3 years, results of single-cell transcriptomics are beginning to reveal cell heterogeneity and early developmental trajectories. Equating this information with the in vivo location of cells and their lineage history is a current challenge. Characterization of the progenitor cells that form the heart and of the gene regulatory networks that control their deployment is of major importance for understanding the origin of congenital heart malformations and for producing cardiac tissue for use in regenerative medicine.
哺乳动物心脏的功能取决于不同心脏细胞类型之间的相互作用。这些细胞的部署,具有精确的时空调节,在发育过程中对于建立心脏结构也很重要。在这篇综述中,我们讨论了心脏细胞类型的不同起源,以及给定类型的细胞之间的谱系关系,这些关系有助于心脏的不同部分。新兴的谱系树显示了细胞命运多样化的进展,模式形成线索先于细胞类型分离,以及趋同点,具有重叠谱系的细胞有助于给定的组织。已经鉴定出几种细胞谱系标记物。然而,与克隆分析相比,在遗传追踪实验中需要谨慎。对细胞群体的遗传研究为谱系决策的机制提供了见解。在过去的 3 年中,单细胞转录组学的结果开始揭示细胞异质性和早期发育轨迹。将这些信息与细胞的体内位置及其谱系历史等同起来是当前的一个挑战。心脏形成的祖细胞的特征及其控制其部署的基因调控网络的特征对于理解先天性心脏畸形的起源和产生用于再生医学的心脏组织非常重要。