从心脏中汲取的经验:在心脏发育过程中模拟电生理特征,以体外分化干细胞来源的心肌细胞。
Lessons from the heart: mirroring electrophysiological characteristics during cardiac development to in vitro differentiation of stem cell derived cardiomyocytes.
机构信息
Department of Medical Physiology, Division of Heart & Lungs, University Medical Center Utrecht, Utrecht, The Netherlands.
Genome Institute of Singapore, 60 Biopolis street, Singapore 138672, Singapore.
出版信息
J Mol Cell Cardiol. 2014 Feb;67:12-25. doi: 10.1016/j.yjmcc.2013.12.011. Epub 2013 Dec 23.
The ability of human pluripotent stem cells (hPSCs) to differentiate into any cell type of the three germ layers makes them a very promising cell source for multiple purposes, including regenerative medicine, drug discovery, and as a model to study disease mechanisms and progression. One of the first specialized cell types to be generated from hPSC was cardiomyocytes (CM), and differentiation protocols have evolved over the years and now allow for robust and large-scale production of hPSC-CM. Still, scientists are struggling to achieve the same, mainly ventricular, phenotype of the hPSC-CM in vitro as their adult counterpart in vivo. In vitro generated cardiomyocytes are generally described as fetal-like rather than adult. In this review, we compare the in vivo development of cardiomyocytes to the in vitro differentiation of hPSC into CM with focus on electrophysiology, structure and contractility. Furthermore, known epigenetic changes underlying the differences between adult human CM and CM differentiated from pluripotent stem cells are described. This should provide the reader with an extensive overview of the current status of human stem cell-derived cardiomyocyte phenotype and function. Additionally, the reader will gain insight into the underlying signaling pathways and mechanisms responsible for cardiomyocyte development.
人多能干细胞(hPSCs)分化为三个胚层的任何细胞类型的能力使它们成为多种用途的非常有前途的细胞来源,包括再生医学、药物发现,以及作为研究疾病机制和进展的模型。最早从 hPSC 中生成的特化细胞类型之一是心肌细胞(CM),并且分化方案多年来一直在发展,现在允许大规模、高效地生产 hPSC-CM。尽管如此,科学家们仍在努力在体外实现与体内成年 hPSC-CM 相同的主要心室表型。在体外产生的心肌细胞通常被描述为类胎儿,而不是成年。在这篇综述中,我们将 hPSC 体外分化为 CM 的过程与体内心肌细胞的发育进行了比较,重点关注了电生理学、结构和收缩性。此外,还描述了导致成年人心肌细胞与多能干细胞分化而来的 CM 之间差异的已知表观遗传变化。这应该为读者提供对人干细胞衍生的心肌细胞表型和功能的当前状况的广泛概述。此外,读者将深入了解负责心肌细胞发育的潜在信号通路和机制。