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诱导鼠胚胎干细胞和诱导多能干细胞向神经元定向分化及其基因表达谱。

Directed neuronal differentiation of mouse embryonic and induced pluripotent stem cells and their gene expression profiles.

机构信息

Laboratory of Developmental Biology, Institute of Medical Science, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China.

出版信息

Int J Mol Med. 2013 Jul;32(1):25-34. doi: 10.3892/ijmm.2013.1372. Epub 2013 May 8.

DOI:10.3892/ijmm.2013.1372
PMID:23652807
Abstract

Embryonic stem cells (ESCs) may be useful as a therapeutic source of cells for the production of healthy tissue; however, they are associated with certain challenges including immunorejection as well as ethical issues. Induced pluripotent stem cells (iPSCs) are a promising substitute since a patient's own adult cells would serve as tissue precursors. Ethical concerns prevent a full evaluation of the developmental potency of human ESCs and iPSCs, therefore, mouse iPSC models are required for protocol development and safety assessments. We used a modified culturing protocol to differentiate pluripotent cells from a mouse iPS cell line and two mouse ES cell lines into neurons. Our results indicated that all three pluripotent stem cell lines underwent nearly the same differentiation process when induced to form neurons in vitro. Genomic expression microarray profiling and single-cell RT-qPCR were used to analyze the neural lineage differentiation process, and more than one thousand differentially expressed genes involved in multiple molecular processes relevant to neural development were identified.

摘要

胚胎干细胞 (ESCs) 可能可作为产生健康组织的细胞治疗来源,但它们与某些挑战相关,包括免疫排斥和伦理问题。诱导多能干细胞 (iPSCs) 是一种很有前途的替代品,因为患者自身的成体细胞将作为组织前体。伦理问题阻止了对人类 ESCs 和 iPSCs 的发育潜力进行全面评估,因此需要使用小鼠 iPSC 模型进行方案开发和安全性评估。我们使用改良的培养方案,将来自小鼠 iPSC 系和两个小鼠 ES 细胞系的多能细胞分化为神经元。我们的结果表明,当在体外诱导这三种多能干细胞系形成神经元时,它们都经历了几乎相同的分化过程。我们使用基因组表达微阵列分析和单细胞 RT-qPCR 来分析神经谱系分化过程,鉴定了 1000 多个涉及多个与神经发育相关的分子过程的差异表达基因。

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