Muotri Alysson R, Nakashima Kinichi, Toni Nicolas, Sandler Vladislav M, Gage Fred H
Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Proc Natl Acad Sci U S A. 2005 Dec 20;102(51):18644-8. doi: 10.1073/pnas.0509315102. Epub 2005 Dec 13.
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.
人类胚胎干细胞是多能的实体,理论上能够产生全身范围内各种不同的细胞类型。然而,这些细胞的分化仅在培养过程中或畸胎瘤形成期间被观察到。我们的结果表明,植入胚胎小鼠脑室的人类胚胎干细胞能够分化为功能性神经谱系,并产生成熟、活跃的人类神经元,这些神经元成功整合到成年小鼠前脑中。此外,这项研究揭示了在整个哺乳动物进化过程中神经分化共同信号的保守性和识别。嵌合模型将允许在活体环境中研究人类神经发育,为生成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。