Morita Yuika, Tohyama Shugo
Department of Cardiology, Keio University School of Medicine, Tokyo, Japan.
Department of Organ Fabrication, Keio University School of Medicine, Tokyo, Japan.
JMA J. 2020 Jul 15;3(3):193-200. doi: 10.31662/jmaj.2020-0036. Epub 2020 Jul 13.
The heart, one of the more complex organs, is composed from a number of differentiated cells. In general, researchers consider that the cardiac cells are derived from the same origin as mesodermal cells, except neural crest cells. However, as the developmental stages proceed, cardiac mesodermal cells are differentiated into various types of cells via cardiac progenitors and demonstrate different programming in transcriptional network and epigenetic regulation in a spatiotemporal manner. In fact, the metabolic feature also changes dramatically during heart development and cardiac differentiation. Researchers reported that each type of cell exhibits different metabolic features that can be used to specifically identify them. Metabolism is a critical process for generating energy and biomass in all living cells and organisms and has been long regarded as a passenger, rather than an active driver, for intracellular status. However, recent studies revealed that metabolism influences self-renewal and cell fate specification via epigenetic changes directly or indirectly. Metabolism mirrors the physiological status of the cell and endogenous cellular activity; therefore, understanding the metabolic signature of each cell type serves as a guide for innovative methods of selecting and differentiating desired cell types. Stem cell biology and developmental biology hold great promise for cardiac regenerative therapy, for which, successful strategy depends on the precise translation of the philosophy of cardiac development in the early embryo to the cell production system. In this review, we focus on the metabolism during heart development and cardiac differentiation and discuss the next challenge to unlock the potential of cell biology for regenerative therapy based on metabolism.
心脏是较为复杂的器官之一，由许多分化细胞组成。一般来说，研究人员认为，除神经嵴细胞外，心脏细胞与中胚层细胞起源相同。然而，随着发育阶段的推进，心脏中胚层细胞通过心脏祖细胞分化为各种类型的细胞，并在转录网络和表观遗传调控中以时空方式表现出不同的编程。事实上，在心脏发育和心脏分化过程中，代谢特征也会发生显著变化。研究人员报告称，每种类型的细胞都表现出不同的代谢特征，可用于特异性识别它们。代谢是所有活细胞和生物体中产生能量和生物量的关键过程，长期以来一直被视为细胞内状态的“乘客”，而非主动驱动因素。然而，最近的研究表明，代谢直接或间接地通过表观遗传变化影响自我更新和细胞命运决定。代谢反映了细胞的生理状态和内源性细胞活动；因此，了解每种细胞类型的代谢特征可为选择和分化所需细胞类型的创新方法提供指导。干细胞生物学和发育生物学对心脏再生治疗具有巨大潜力，为此，成功的策略取决于将早期胚胎中心脏发育的理念精确转化为细胞生产系统。在本综述中，我们聚焦于心脏发育和心脏分化过程中的代谢，并讨论基于代谢释放细胞生物学用于再生治疗潜力的下一个挑战。
