title: A Robust Single Primate Neuroepithelial Cell Clonal Expansion System for Neural Tube Development and Disease Studies.
abstract: Developing a model of primate neural tube (NT) development is important to promote many NT disorder studies in model organisms. Here, we report a robust and stable system to allow for clonal expansion of single monkey neuroepithelial stem cells (NESCs) to develop into miniature NT-like structures. Single NESCs can produce functional neurons in vitro, survive, and extensively regenerate neuron axons in monkey brain. NT formation and NESC maintenance depend on high metabolism activity and Wnt signaling. NESCs are regionally restricted to a telencephalic fate. Moreover, single NESCs can turn into radial glial progenitors (RGPCs). The transition is accurately regulated by Wnt signaling through regulation of Notch signaling and adhesion molecules. Finally, using the "NESC-TO-NTs" system, we model the functions of folic acid (FA) on NT closure and demonstrate that FA can regulate multiple mechanisms to prevent NT defects. Our system is ideal for studying NT development and diseases.
authors.affiliation: Yunnan Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, 650500 Yunnan, China; National Engineering Research Center of Biomedicine and Animal Science, Kunming 650500, 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, 650500 Yunnan, China; Chongqing Key Lab of Forage & Herbivore, College of Animal Science and Technology (CAST), Southwest University, No. 1 Tiansheng Road, Beibei, Chongqing 400715, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.affiliation: Yunnan Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, 650500 Yunnan, China; National Engineering Research Center of Biomedicine and Animal Science, Kunming 650500, China.
authors.forename: Zongyong
authors.initials: Z
authors.lastname: Ai
authors.affiliation: Yunnan Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, 650500 Yunnan, China; Chongqing Key Lab of Forage & Herbivore, College of Animal Science and Technology (CAST), Southwest University, No. 1 Tiansheng Road, Beibei, Chongqing 400715, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Xiang
authors.affiliation: Translational Stem Cell Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai 200092, China.
authors.forename: Kunshang
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Yunnan Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, 650500 Yunnan, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Qiu
authors.affiliation: Yunnan Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, 650500 Yunnan, China; National Engineering Research Center of Biomedicine and Animal Science, Kunming 650500, China.
authors.forename: Yongchang
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Chongqing Key Lab of Forage & Herbivore, College of Animal Science and Technology (CAST), Southwest University, No. 1 Tiansheng Road, Beibei, Chongqing 400715, China.
authors.forename: Yuemin
authors.initials: Y
authors.lastname: Li
authors.affiliation: Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223 Yunnan, China.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Rizak
authors.affiliation: Yunnan Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, 650500 Yunnan, China; National Engineering Research Center of Biomedicine and Animal Science, Kunming 650500, China.
authors.forename: Yuyu
authors.initials: Y
authors.lastname: Niu
authors.affiliation: Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223 Yunnan, 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, 650500 Yunnan, China; Translational Stem Cell Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai 200092, China.
authors.forename: Yi Eve
authors.initials: YE
authors.lastname: Sun
authors.affiliation: Yunnan Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, 650500 Yunnan, China; National Engineering Research Center of Biomedicine and Animal Science, Kunming 650500, China. Electronic address: wji@kbimed.com.
authors.forename: Weizhi
authors.initials: W
authors.lastname: Ji
authors.affiliation: Yunnan Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, 650500 Yunnan, China; National Engineering Research Center of Biomedicine and Animal Science, Kunming 650500, China. Electronic address: litq@kbimed.com.
authors.forename: Tianqing
authors.initials: T
authors.lastname: Li
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D018929:Cell Culture Techniques / Q000379:methods*; D019070:Cell Lineage; D049109:Cell Proliferation; D002999:Clone Cells; D004195:Disease Models, Animal; D005494:Folic Acid Deficiency / Q000473:pathology; D008253:Macaca mulatta; D054259:Neural Tube / Q000196:embryology* / Q000473:pathology*; D009436:Neural Tube Defects / Q000473:pathology*; D046569:Neuroepithelial Cells / Q000166:cytology*; D009457:Neuroglia / Q000166:cytology; D009474:Neurons / Q000166:cytology; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D013687:Telencephalon / Q000166:cytology; D060449:Wnt Signaling Pathway