title: Efficient Generation of Corticofugal Projection Neurons from Human Embryonic Stem Cells.
abstract: Efforts to study development and function of corticofugal projection neurons (CfuPNs) in the human cerebral cortex for health and disease have been limited by the unavailability of highly enriched CfuPNs. Here, we develop a robust, two-step process for generating CfuPNs from human embryonic stem cells (hESCs): directed induction of neuroepithelial stem cells (NESCs) from hESCs and efficient differentiation of NESCs to about 80% of CfuPNs. NESCs or a NESC faithfully maintain unlimitedly self-renewal and self-organized abilities to develop into miniature neural tube-like structures. NESCs retain a stable propensity toward neuronal differentiation over culture as fate-restricted progenitors of CfuPNs and interneurons. When grafted into mouse brains, NESCs successfully integrate into the host brains, differentiate into CfuPNs and effectively reestablish specific patterns of subcortical projections and synapse structures. Efficient generation of CfuPNs in vitro and in vivo will facilitate human cortex development and offer sufficient CfuPNs for cell therapy.
authors.affiliation: School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230000, PR China.|Yunnan Key Laboratory of Primate Biomedical Research; Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan 650500, China.|Kunming Ennovate Institute of Bioscience, Kunming, Yunnan 650500, China.|Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences &Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan 650223, China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Yunnan Key Laboratory of Primate Biomedical Research; Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan 650500, China.|Kunming Ennovate Institute of Bioscience, Kunming, Yunnan 650500, China.
authors.forename: Zongyong
authors.initials: Z
authors.lastname: Ai
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences &Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan 650223, China.
authors.forename: Xintian
authors.initials: X
authors.lastname: Hu
authors.affiliation: Yunnan Key Laboratory of Primate Biomedical Research; Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan 650500, China.|Kunming Ennovate Institute of Bioscience, Kunming, Yunnan 650500, China.
authors.forename: Tianqing
authors.initials: T
authors.lastname: Li
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000502:physiology; D000066449:Human Embryonic Stem Cells / Q000502:physiology*; D006801:Humans; D007395:Interneurons / Q000502:physiology; D051379:Mice; D054259:Neural Tube / Q000502:physiology; D046569:Neuroepithelial Cells / Q000502:physiology; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000502:physiology*