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将淋巴母细胞源性诱导多能干细胞分化为功能性心肌细胞、神经元和肌母细胞。

Differentiation of lymphoblastoid-derived iPSCs into functional cardiomyocytes, neurons and myoblasts.

机构信息

CERVO Brain Research Center, Institut Universitaire en santé mentale de Québec, Quebec City, QC, G1J 2G3, Canada.

Human Genetics Unit, Laboratoire d'Organogénèse Experimentale (LOEX). Hôpital de l'Enfant-Jésus, CHU Research Center, Quebec City, QC, G1J 1Z4, Canada.

出版信息

Biochem Biophys Res Commun. 2019 Aug 13;516(1):222-228. doi: 10.1016/j.bbrc.2019.05.176. Epub 2019 Jun 14.

DOI:10.1016/j.bbrc.2019.05.176
PMID:31208718
Abstract

Human induced pluripotent stem cells (hiPSCs) are a valuable tool for investigating complex cellular and molecular events that occur in several human diseases. Importantly, the ability to differentiate hiPSCs into any human cell type provides a unique way for investigating disease mechanisms such as complex mental health diseases. The in vitro transformation of human lymphocytes into lymphoblasts (LCLs) using the Epstein-Barr virus (EBV) has been the main method for generating immortalized human cell lines for half a century. However, the derivation of iPSCs from LCLs has emerged as an alternative source from which these cell lines can be generated. We show that iPSCs derived from LCLs using the Sendai virus procedure can be successfully differentiated into cardiomyocytes, neurons, and myotubes that express neuron- and myocyte-specific markers. We further show that these cardiac and neuronal cells are functional and generate action potentials that are required for cell excitability. We conclude that the ability to differentiate LCLs into neurons and myocytes will increase the use of LCLs in the future as a potential source of cells for modelling a number of diseases.

摘要

人类诱导多能干细胞(hiPSCs)是研究多种人类疾病中发生的复杂细胞和分子事件的有价值的工具。重要的是,将 hiPSCs 分化为任何人类细胞类型的能力为研究复杂的精神疾病等疾病机制提供了一种独特的方法。使用 Epstein-Barr 病毒(EBV)将人类淋巴细胞体外转化为淋巴母细胞(LCL)的方法已经成为生成永生人类细胞系的主要方法半个世纪。然而,从 LCL 中提取 iPSCs 已经成为生成这些细胞系的替代来源。我们表明,使用 Sendai 病毒程序从 LCL 中提取的 iPSCs 可以成功分化为心肌细胞、神经元和肌管,这些细胞表达神经元和肌细胞特异性标记物。我们进一步表明,这些心脏和神经元细胞具有功能并且产生动作电位,这是细胞兴奋性所必需的。我们的结论是,将 LCL 分化为神经元和肌细胞的能力将增加未来 LCL 作为多种疾病模型细胞的潜在来源的使用。

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