Tsunemoto Rachel K, Eade Kevin T, Blanchard Joel W, Baldwin Kristin K
The Scripps Research Institute, La Jolla, CA, USA.
The Scripps Research Institute, La Jolla, CA, USA
EMBO J. 2015 Jun 3;34(11):1445-55. doi: 10.15252/embj.201591402. Epub 2015 Apr 23.
The nervous system is comprised of a vast diversity of distinct neural cell types. Differences between neuronal subtypes drive the assembly of neuronal circuits and underlie the subtype specificity of many neurological diseases. Yet, because neurons are irreversibly post-mitotic and not readily available from patients, it has not been feasible to study specific subtypes of human neurons in larger numbers. A powerful means to study neuronal diversity and neurological disease is to establish methods to produce desired neuronal subtypes in vitro. Traditionally this has been accomplished by treating pluripotent or neural stem cells with growth factors and morphogens that recapitulate exogenous developmental signals. These approaches often require extended periods of culture, which can limit their utility. However, more recently, it has become possible to produce neurons directly from fibroblasts using transcription factors and/or microRNAs. This technique referred to as direct reprogramming or transdifferentiation has proven to be a rapid, robust, and reproducible method to generate mature neurons of many different subtypes from multiple cell sources. Here, we highlight recent advances in generating neurons of specific subtypes using direct reprogramming and outline various scenarios in which induced neurons may be applied to studies of neuronal function and neurological disease.
神经系统由种类繁多、各不相同的神经细胞类型组成。神经元亚型之间的差异驱动着神经回路的组装，也是许多神经系统疾病亚型特异性的基础。然而，由于神经元在有丝分裂后不可逆转，且难以从患者身上获取，因此大量研究人类神经元的特定亚型并不可行。研究神经元多样性和神经系统疾病的一个有效方法是建立在体外产生所需神经元亚型的方法。传统上，这是通过用生长因子和形态发生素来处理多能干细胞或神经干细胞来实现的，这些生长因子和形态发生素可重现外源性发育信号。这些方法通常需要长时间培养，这可能会限制它们的实用性。然而，最近，利用转录因子和/或微小RNA直接从成纤维细胞产生神经元已成为可能。这种被称为直接重编程或转分化的技术已被证明是一种快速、强大且可重复的方法，可从多种细胞来源生成许多不同亚型的成熟神经元。在这里，我们重点介绍了利用直接重编程生成特定亚型神经元的最新进展，并概述了诱导神经元可应用于神经元功能和神经系统疾病研究的各种情况。
