Department of Psychiatry, Weill Cornell Medical College New York, NY, USA.
Front Mol Neurosci. 2011 Oct 12;4:30. doi: 10.3389/fnmol.2011.00030. eCollection 2011.
The mammalian central nervous system is a complex neuronal network consisting of a diverse array of cellular subtypes generated in a precise spatial and temporal pattern throughout development. Achieving a greater understanding of the molecular and genetic mechanisms that direct a relatively uniform population of neuroepithelial progenitors into diverse neuronal subtypes remains a significant challenge. The advent of pluripotent stem cell (PSC) technology allows researchers to generate diverse neural populations in vitro. Although the primary focus of PSC-derived neural cells has been their therapeutic potential, utilizing PSCs to study neurodevelopment is another frequently overlooked and equally important application. In this review, we explore the potential for utilizing PSCs to study neural development. We introduce the types of neurodevelopmental questions that PSCs can help to address, and we discuss the different strategies and technologies that researchers use to generate diverse subtypes of PSC-derived neurons. Additionally, we highlight the derivation of several thoroughly characterized neural subtypes; spinal motoneurons, midbrain dopaminergic neurons and cortical neurons. We hope that this review encourages researchers to develop innovative strategies for using PSCs for the study of mammalian, and specifically human, neurodevelopment.
哺乳动物中枢神经系统是一个复杂的神经元网络,由在发育过程中以精确的时空模式产生的各种细胞亚型组成。深入了解指导相对均匀的神经上皮祖细胞分化为多种神经元亚型的分子和遗传机制仍然是一个重大挑战。多能干细胞(PSC)技术的出现使研究人员能够在体外产生多种神经群体。尽管 PSC 衍生的神经细胞的主要重点是它们的治疗潜力,但利用 PSCs 研究神经发育是另一个经常被忽视但同样重要的应用。在这篇综述中,我们探讨了利用 PSCs 研究神经发育的潜力。我们介绍了 PSCs 可以帮助解决的神经发育问题的类型,并讨论了研究人员用于生成多种 PSC 衍生神经元亚型的不同策略和技术。此外,我们还重点介绍了几种经过彻底表征的神经亚型的衍生,包括脊髓运动神经元、中脑多巴胺能神经元和皮质神经元。我们希望这篇综述鼓励研究人员开发创新策略,利用 PSCs 研究哺乳动物,特别是人类的神经发育。