Neural differentiation of human induced pluripotent stem cells follows developmental principles but with variable potency

Neural differentiation of human induced pluripotent stem cells follows developmental principles but with variable potency
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DOI:
10.1073/pnas.0910012107
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发表时间:
2010-03-02
影响因子:
11.1
通讯作者:
Zhang, Su-Chun
Zhang, Su-Chun
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Hu, Bao-Yang;Weick, Jason P.;Zhang, Su-Chun

文献摘要

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为了实现人类诱导多能干细胞(iPSCs)的前景,有必要研究它们是否以及如何有效地分化为各种谱系的功能细胞。在这里,我们直接比较了人类多能干细胞和胚胎干细胞(ESCs)的神经分化能力。我们已经证明,人类iPSCs使用相同的转录网络来产生神经上皮细胞和功能合适的神经元类型,在相同的发育时间过程中,与hESCs响应相同的一组形态因子;然而,他们这样做的效率显著降低,可变性增加。这些结果在不同的iPSC系中是一致的,并且与用于获得iPSC的重编程转基因集以及iPSC中存在或不存在重编程转基因无关。这些发现表明需要提高iPSCs的分化能力,这表明在病理研究、治疗筛选和自体细胞移植中使用人iPSCs是可能的。
For the promise of human induced pluripotent stem cells (iPSCs) to be realized, it is necessary to ask if and how efficiently they may be differentiated to functional cells of various lineages. Here, we have directly compared the neural-differentiation capacity of human iPSCs and embryonic stem cells (ESCs). We have shown that human iPSCs use the same transcriptional network to generate neuroepithelia and functionally appropriate neuronal types over the same developmental time course as hESCs in response to the same set of morphogens; however, they do it with significantly reduced efficiency and increased variability. These results were consistent across iPSC lines and independent of the set of reprogramming transgenes used to derive iPSCs as well as the presence or absence of reprogramming transgenes in iPSCs. These findings, which show a need for improving differentiation potency of iPSCs, suggest the possibility of employing human iPSCs in pathological studies, therapeutic screening, and autologous cell transplantation.