Department of Biochemistry, Wellcome Trust Centre for Stem Cell Research, University of Cambridge, Cambridge, United Kingdom.
PLoS One. 2012;7(1):e29597. doi: 10.1371/journal.pone.0029597. Epub 2012 Jan 17.
Human embryonic stem cells (hESC) and induced pluripotent stem cells (iPSC) provide new prospects for studying human neurodevelopment and modeling neurological disease. In particular, iPSC-derived neural cells permit a direct comparison of disease-relevant molecular pathways in neurons and glia derived from patients and healthy individuals. A prerequisite for such comparative studies are robust protocols that efficiently yield standardized populations of neural cell types. Here we show that long-term self-renewing neuroepithelial-like stem cells (lt-NES cells) derived from 3 hESC and 6 iPSC lines in two independent laboratories exhibit consistent characteristics including i) continuous expandability in the presence of FGF2 and EGF; ii) stable neuronal and glial differentiation competence; iii) characteristic transcription factor profile; iv) hindbrain specification amenable to regional patterning; v) capacity to generate functionally mature human neurons. We further show that lt-NES cells are developmentally distinct from fetal tissue-derived radial glia-like stem cells. We propose that lt-NES cells provide an interesting tool for studying human neurodevelopment and may serve as a standard system to facilitate comparative analyses of hESC and hiPSC-derived neural cells from control and diseased genetic backgrounds.
人类胚胎干细胞（hESC）和诱导多能干细胞（iPSC）为研究人类神经发育和神经疾病模型提供了新的前景。特别是，iPSC 衍生的神经细胞允许在源自患者和健康个体的神经元和神经胶质中直接比较与疾病相关的分子途径。进行此类比较研究的前提是具有高效产生标准化神经细胞类型群体的稳健方案。在这里，我们展示了来自两个独立实验室的 3 个 hESC 和 6 个 iPSC 系中衍生的长期自我更新的神经上皮样干细胞（lt-NES 细胞）具有一致的特征，包括 i）在 FGF2 和 EGF 的存在下具有连续的可扩展性；ii）稳定的神经元和神经胶质分化能力；iii）特征性转录因子谱；iv）易于进行区域模式化的后脑特异性；v）生成功能成熟的人类神经元的能力。我们进一步表明，lt-NES 细胞在发育上与源自胎儿组织的放射状胶质样干细胞不同。我们提出，lt-NES 细胞为研究人类神经发育提供了一个有趣的工具，并可能作为一种标准系统，促进来自对照和患病遗传背景的 hESC 和 hiPSC 衍生的神经细胞的比较分析。
