Dang Lan, Tropepe Vincent
Department of Cell & Systems Biology, University of Toronto, ON, Canada.
Regen Med. 2006 Sep;1(5):635-52. doi: 10.2217/17460751.1.5.635.
Embryonic stem (ES) cells are a pluripotent and renewable cellular resource with tremendous potential for broad applications in regenerative medicine. Arguably the most important consideration for stem cell-based therapies is the ability to precisely direct the differentiation of stem cells along a preferred cellular lineage. During development, lineage commitment is a multistep process requiring the activation and repression of sets of genes at various stages, from an ES cell identity to a tissue-specific stem cell identity and beyond. Thus, the challenge is to ensure that the pattern of genomic regulation is recapitulated during the in vitro differentiation of ES cells into stem/progenitor cells of the appropriate tissue in a robust, predictable and stable manner. To address this issue, we must understand the ontogeny of tissue-specific stem cells during normal embryogenesis and compare the ontogeny of tissue-specific stem cells in ES cell models. Here, we discuss the issue of directed differentiation of pluripotent ES cells into neural stem cells, which is fundamentally linked to two early events in the development of the mammalian nervous system: the 'decision' of the ectoderm to acquire a neural identity (neural determination) and the origin of neural stem cells within this neural-committed population of cells. A clearer understanding of the molecular and cellular mechanisms that govern mammalian neural cell fate determination will lead to improved ES technology applications in neural regeneration.
胚胎干细胞（ES细胞）是一种多能且可再生的细胞资源，在再生医学中具有广泛应用的巨大潜力。可以说，基于干细胞的疗法最重要的考虑因素是能够精确地引导干细胞沿着优选的细胞谱系分化。在发育过程中，谱系定向是一个多步骤过程，需要在从ES细胞特性到组织特异性干细胞特性及其他阶段的各个阶段激活和抑制多组基因。因此，挑战在于确保在将ES细胞体外分化为适当组织的干细胞/祖细胞的过程中，以稳健、可预测和稳定的方式重现基因组调控模式。为了解决这个问题，我们必须了解正常胚胎发生过程中组织特异性干细胞的个体发育，并比较ES细胞模型中组织特异性干细胞的个体发育。在这里，我们讨论多能ES细胞定向分化为神经干细胞的问题，这与哺乳动物神经系统发育中的两个早期事件有根本联系：外胚层“决定”获得神经特性（神经决定）以及在这个神经定向细胞群体中神经干细胞的起源。对控制哺乳动物神经细胞命运决定的分子和细胞机制有更清晰的理解将有助于改进ES技术在神经再生中的应用。
