通过定义的转录因子诱导人类神经元细胞
Zhiping P Pang1, Nan Yang, Thomas Vierbuchen
1Department of Molecular and Cellular Physiology, Stanford University School of Medicine, 265 Campus Drive, Stanford, California 94305, USA.
Nature
|May 28, 2011
概括
研究人员使用三个特定的转录因子将人体细胞转化为功能神经元. 这一突破为产生患者特异的神经元的新方法提供了新的方法,用于疾病建模和再生医学.
科学领域:
- 神经科学是一个神经科学.
- 干细胞生物学 干细胞生物学
- 细胞重编程 细胞重编程
背景情况:
- 细胞酸盐变化可以通过各种方法诱导,包括转录因子表达.
- 之前的研究表明,使用Brn2,Ascl1和Myt1l,小鼠纤维细胞被有效地转化为诱导的神经元 (iN) 细胞.
- 人类细胞重新编程成功能神经元仍然是再生医学的一个重大挑战.
研究的目的:
- 研究一种特定的转录因子组合在将人体体和多能细胞转化为功能神经元的有效性.
- 评估生成的人类IN细胞的神经元特征,成熟和功能潜力.
- 建立一种强大的方法来产生患者特异的人类神经元,用于研究和治疗应用.
主要方法:
- 在人类多能干细胞中强制表达转录因子Brn2 (Pou3f2),Ascl1和Myt1l.
- 与Brn2,Ascl1和Myt1l共同表达NeuroD1,以转化人类胎儿和产后纤维细胞.
- 评估神经元形态,标记物表达,动作潜能生成和突触集成.
主要成果:
- 功能神经元 (iN细胞) 由人类多能干细胞生成,在转基因激活后6天内产生.
- 人体纤维细胞成功地转化为表现出神经元形态和标记的IN细胞,即使在降低因子调节后也是如此.
- 大多数人体IN细胞在与主要神经元共同培养时产生动作潜力并形成突触联系.
结论:
- 确定血统的转录因子可以直接将非神经的人体体细胞和多能干细胞转化为功能神经元.
- 这种直接重编程方法为生成患者特定的人类神经元提供了强大的工具.
- 这些发现对推进体外疾病建模和再生医学策略具有重大前景.
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