Development of functional human embryonic stem cell-derived neurons in mouse brain

Development of functional human embryonic stem cell-derived neurons in mouse brain
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DOI:
10.1073/pnas.0509315102
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发表时间:
2005-12-20
影响因子:
11.1
通讯作者:
Gage, FH
Gage, FH
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Muotri, AR;Nakashima, K;Gage, FH

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人类胚胎干细胞是多能实体,理论上能够产生不同细胞类型的全身光谱。然而,只有在培养或畸胎瘤形成期间才能观察到这些细胞的分化。我们的结果表明,植入胚胎小鼠脑室的人类胚胎干细胞可以分化为功能神经系,并生成成熟、活跃的人类神经元,成功整合到成年小鼠的前脑中。此外,这项研究揭示了哺乳动物进化过程中神经分化的共同信号的保守和识别。该嵌合模型将允许在活体环境中研究人类神经发育,为产生人类神经退行性疾病和精神疾病的新模型铺平道路。该模型还有可能加快治疗药物的筛选过程。
Human embryonic stem cells are pluripotent entities, theoretically capable of generating a whole-body spectrum of distinct cell types. However, differentiation of these cells has been observed only in culture or during teratoma formation. Our results show that human embryonic stem cells implanted in the brain ventricles of embryonic mice can differentiate into functional neural lineages and generate mature, active human neurons that successfully integrate into the adult mouse forebrain. Moreover, this study reveals the conservation and recognition of common signals for neural differentiation throughout mammalian evolution. The chimeric model will permit the study of human neural development in a live environment, paving the way for the generation of new models of human neurodegenerative and psychiatric diseases. The model also has the potential to speed up the screening process for therapeutic drugs.