Mitochondria and metabolic transitions in cardiomyocytes: lessons from development for stem cell-derived cardiomyocytes.
Mitochondria and metabolic transitions in cardiomyocytes: lessons from development for stem cell-derived cardiomyocytes.
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心肌细胞的线粒体和代谢转变：干细胞衍生心肌细胞发育的经验教训。
DOI：
10.1186/s13287-021-02252-6
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发表时间：
2021-03-12
影响因子：
7.5
通讯作者：
Lee RT
中科院分区：
文献类型：
--
作者：
Garbern JC;Lee RT
目前将心肌细胞与人类多能干细胞 (PSC) 区分开来的方法不足以重现完整的发育，并导致 PSC 衍生的心肌细胞 (PSC-CM) 具有不成熟或胎儿样表型。胚胎和胎儿发育是高度动态的时期，在此期间，发育中的胚胎或胎儿在出生之前暴露于不断变化的营养、氧气和激素水平。越来越明显的是，这些代谢变化启动了成熟心肌细胞的发育过程。线粒体是这些变化的核心，它对这些代谢变化做出反应，并从小、碎片化的线粒体转变为能够产生足够 ATP 来支持心脏收缩功能的大型细胞器。线粒体的这些变化可能不仅仅是对心肌细胞成熟的反应；整个发育过程中发生的代谢信号实际上可能是心肌细胞成熟过程的核心。在这里，我们回顾了促进 PSC-CM 成熟的方法，并重点介绍了表明线粒体在心肌细胞成熟过程中发挥关键作用的发育证据。我们评估发育过程中发生的代谢转变以及这些转变如何影响分子营养传感器，讨论营养传感途径的调节如何影响线粒体动力学和功能，并探索线粒体功能的变化如何影响代谢物产生、细胞周期和表观遗传学，从而影响心肌细胞的成熟。
Current methods to differentiate cardiomyocytes from human pluripotent stem cells (PSCs) inadequately recapitulate complete development and result in PSC-derived cardiomyocytes (PSC-CMs) with an immature or fetal-like phenotype. Embryonic and fetal development are highly dynamic periods during which the developing embryo or fetus is exposed to changing nutrient, oxygen, and hormone levels until birth. It is becoming increasingly apparent that these metabolic changes initiate developmental processes to mature cardiomyocytes. Mitochondria are central to these changes, responding to these metabolic changes and transitioning from small, fragmented mitochondria to large organelles capable of producing enough ATP to support the contractile function of the heart. These changes in mitochondria may not simply be a response to cardiomyocyte maturation; the metabolic signals that occur throughout development may actually be central to the maturation process in cardiomyocytes. Here, we review methods to enhance maturation of PSC-CMs and highlight evidence from development indicating the key roles that mitochondria play during cardiomyocyte maturation. We evaluate metabolic transitions that occur during development and how these affect molecular nutrient sensors, discuss how regulation of nutrient sensing pathways affect mitochondrial dynamics and function, and explore how changes in mitochondrial function can affect metabolite production, the cell cycle, and epigenetics to influence maturation of cardiomyocytes.
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影响因子：
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