title: Generation and expansion of highly pure motor neuron progenitors from human pluripotent stem cells.
abstract: Human pluripotent stem cells (hPSCs) have opened new opportunities for understanding human development, modelling disease processes and developing new therapeutics. However, these applications are hindered by the low efficiency and heterogeneity of cell types, such as motorneurons (MNs), differentiated from hPSCs as well as our inability to maintain the potency of lineage-committed progenitors. Here by using a combination of small molecules that regulate multiple signalling pathways, we develop a method to guide human embryonic stem cells to a near-pure population (>95%) of motor neuron progenitors (MNPs) in 12 days, and an enriched population (>90%) of functionally mature MNs in an additional 16 days. More importantly, the MNPs can be expanded for at least five passages so that a single MNP can be amplified to 1 × 10(4). This method is reproducible in human-induced pluripotent stem cells and is applied to model MN-degenerative diseases and in proof-of-principle drug-screening assays.
authors: Waisman Center, University of Wisconsin, Madison, Wisconsin 53705, USA.
authors: Zhong-Wei
authors: ZW
authors: Du
authors: 1] Waisman Center, University of Wisconsin, Madison, Wisconsin 53705, USA [2] Department of Rehabilitation Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors: Hong
authors: H
authors: Chen
authors: Waisman Center, University of Wisconsin, Madison, Wisconsin 53705, USA.
authors: Huisheng
authors: H
authors: Liu
authors: Waisman Center, University of Wisconsin, Madison, Wisconsin 53705, USA.
authors: Jianfeng
authors: J
authors: Lu
authors: 1] Waisman Center, University of Wisconsin, Madison, Wisconsin 53705, USA [2] Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors: Kun
authors: K
authors: Qian
authors: Waisman Center, University of Wisconsin, Madison, Wisconsin 53705, USA.
authors: CindyTzu-Ling
authors: CL
authors: Huang
authors: Waisman Center, University of Wisconsin, Madison, Wisconsin 53705, USA.
authors: Xiaofen
authors: X
authors: Zhong
authors: Promega Corporation, Madison, Wisconsin 53711, USA.
authors: Frank
authors: F
authors: Fan
authors: 1] Waisman Center, University of Wisconsin, Madison, Wisconsin 53705, USA [2] Department of Neuroscience and Department of Neurology, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin 53705, USA.
authors: Su-Chun
authors: SC
authors: Zhang
mesh_terms: D018929:Cell Culture Techniques; D006801:Humans; D009046:Motor Neurons / Q000166:cytology*; D058953:Neural Stem Cells / Q000166:cytology*; D009469:Neuromuscular Junction / Q000166:cytology; D039904:Pluripotent Stem Cells / Q000166:cytology*