Systems Neurobiology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey, Pines Road, La Jolla, California, 92037, USA.
CNS Neurol Disord Drug Targets. 2011 Jun;10(4):419-32. doi: 10.2174/187152711795563958.
Embryonic stem (ES) cells are derived from the inner cell mass (ICM) of blastocyst stage embryos, while induced pluripotent stem (iPS) cells are generated from somatic cells through transient overexpression of defined transcription factors. When transplanted into a preimplantation embryo, ES cells and iPS cells can differentiate into any cell type, including germ cells. Moreover, they can grow in culture indefinitely while maintaining pluripotency. In vitro differentiation of ES cells and iPS cells recapitulates many aspects of in vivo embryogenesis. The acquisition of neural fates (neural induction) in ES cells can be controlled by bone morphogenetic protein (BMP), fibroblast growth factor (FGF), and Wnt signaling, while the production of specific neural cell types (neural patterning) can be controlled by exogenous patterning signals such as Wnt, BMP, Shh, FGF, and retinoic acid. In response to these signals, ES cells can differentiate into a wide range of neural cell types that correlate with their positions along the anterior-posterior and dorsal-ventral axes. ES cell and iPS cell culture systems will provide materials for cell replacement therapy, and can be used as in vitro models for disease and drug testing as well as development. Here we review spatiotemporal control of neural differentiation of mammalian pluripotent stem cells, with a special emphasis on the relationship between in vivo embryogenesis and in vitro ES cell differentiation. Retinal differentiation from ES cells and iPS cells is also outlined.
胚胎干细胞（ES 细胞）来源于囊胚期胚胎的内细胞团（ICM），而诱导多能干细胞（iPS 细胞）则是通过瞬时过表达特定转录因子从体细胞产生的。当移植到着床前胚胎中时，ES 细胞和 iPS 细胞可以分化为任何细胞类型，包括生殖细胞。此外，它们可以在培养中无限期生长，同时保持多能性。ES 细胞和 iPS 细胞的体外分化再现了体内胚胎发生的许多方面。ES 细胞中神经命运的获得（神经诱导）可以通过骨形态发生蛋白（BMP）、成纤维细胞生长因子（FGF）和 Wnt 信号来控制，而特定神经细胞类型的产生（神经模式化）可以通过外源性模式化信号（如 Wnt、BMP、Shh、FGF 和视黄酸）来控制。对这些信号的反应，ES 细胞可以分化为广泛的神经细胞类型，这些类型与它们沿前-后和背-腹轴的位置相关。ES 细胞和 iPS 细胞培养系统将为细胞替代治疗提供材料，并可作为疾病和药物测试以及发育的体外模型。本文综述了哺乳动物多能干细胞神经分化的时空控制，特别强调了体内胚胎发生和体外 ES 细胞分化之间的关系。还概述了从 ES 细胞和 iPS 细胞中进行视网膜分化。
