Erich and Hanna Klessmann Institute, Heart and Diabetes Center NRW, University Hospital of the Ruhr-University Bochum, Georgstrasse 11, D-32545 Bad Oeynhausen, Germany.
Department of Thoracic and Cardiovascular Surgery, Heart and Diabetes Center NRW, University Hospital Ruhr-University Bochum, Georgstrasse 11, D-32545 Bad Oeynhausen, Germany.
Int J Mol Sci. 2019 Sep 6;20(18):4381. doi: 10.3390/ijms20184381.
In the last few decades, many pathogenic or likely pathogenic genetic mutations in over hundred different genes have been described for non-ischemic, genetic cardiomyopathies. However, the functional knowledge about most of these mutations is still limited because the generation of adequate animal models is time-consuming and challenging. Therefore, human induced pluripotent stem cells (iPSCs) carrying specific cardiomyopathy-associated mutations are a promising alternative. Since the original discovery that pluripotency can be artificially induced by the expression of different transcription factors, various patient-specific-induced pluripotent stem cell lines have been generated to model non-ischemic, genetic cardiomyopathies in vitro. In this review, we describe the genetic landscape of non-ischemic, genetic cardiomyopathies and give an overview about different human iPSC lines, which have been developed for the disease modeling of inherited cardiomyopathies. We summarize different methods and protocols for the general differentiation of human iPSCs into cardiomyocytes. In addition, we describe methods and technologies to investigate functionally human iPSC-derived cardiomyocytes. Furthermore, we summarize novel genome editing approaches for the genetic manipulation of human iPSCs. This review provides an overview about the genetic landscape of inherited cardiomyopathies with a focus on iPSC technology, which might be of interest for clinicians and basic scientists interested in genetic cardiomyopathies.
在过去的几十年中，已经在超过一百个不同的基因中描述了许多非缺血性、遗传性心肌病的致病或可能致病的遗传突变。然而，由于生成足够的动物模型既耗时又具有挑战性，因此大多数这些突变的功能知识仍然有限。因此，携带特定心肌病相关突变的人诱导多能干细胞（iPSC）是一种很有前途的替代方法。自从发现不同转录因子的表达可以人为地诱导多能性以来，已经产生了各种患者特异性诱导多能干细胞系，以在体外模拟非缺血性、遗传性心肌病。在这篇综述中，我们描述了非缺血性、遗传性心肌病的遗传景观，并概述了为遗传性心肌病的疾病建模而开发的不同人类 iPSC 系。我们总结了将人类 iPSC 一般分化为心肌细胞的不同方法和方案。此外，我们还描述了用于研究功能上源自人类 iPSC 的心肌细胞的方法和技术。此外，我们还总结了用于人类 iPSC 遗传操作的新型基因组编辑方法。本篇综述提供了一个关于遗传性心肌病的遗传景观概述，重点介绍了 iPSC 技术，这可能对有兴趣研究遗传型心肌病的临床医生和基础科学家感兴趣。
