title: High-efficiency motor neuron differentiation from human pluripotent stem cells and the function of Islet-1.
abstract: Efficient derivation of large-scale motor neurons (MNs) from human pluripotent stem cells is central to the understanding of MN development, modelling of MN disorders in vitro and development of cell-replacement therapies. Here we develop a method for rapid (20 days) and highly efficient (~70%) differentiation of mature and functional MNs from human pluripotent stem cells by tightly modulating neural patterning temporally at a previously undefined primitive neural progenitor stage. This method also allows high-yield (>250%) MN production in chemically defined adherent cultures. Furthermore, we show that Islet-1 is essential for formation of mature and functional human MNs, but, unlike its mouse counterpart, does not regulate cell survival or suppress the V2a interneuron fate. Together, our discoveries improve the strategy for MN derivation, advance our understanding of human neural specification and MN development, and provide invaluable tools for human developmental studies, drug discovery and regenerative medicine.
authors.affiliation: 1] Department of Cell and Developmental Biology, South Goodwin Avenue, Urbana, Illinois 61801, USA [2] Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
authors.forename: Qiuhao
authors.initials: Q
authors.lastname: Qu
authors.affiliation: 1] Department of Cell and Developmental Biology, South Goodwin Avenue, Urbana, Illinois 61801, USA [2] Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
authors.forename: Dong
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Molecular Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
authors.forename: Kathleen R
authors.initials: KR
authors.lastname: Louis
authors.affiliation: 1] Key Laboratory of Environmental and Applied Microbiology, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, China [2] Environmental Microbiology Key Laboratory of Sichuan Province, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, China.
authors.forename: Xiangzhen
authors.initials: X
authors.lastname: Li
authors.affiliation: 1] Department of Cell and Developmental Biology, South Goodwin Avenue, Urbana, Illinois 61801, USA [2] Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Yang
authors.affiliation: 1] Department of Cell and Developmental Biology, South Goodwin Avenue, Urbana, Illinois 61801, USA [2] Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
authors.forename: Qinyu
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Department of Molecular Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
authors.forename: Shane R
authors.initials: SR
authors.lastname: Crandall
authors.affiliation: 1] Department of Cell and Developmental Biology, South Goodwin Avenue, Urbana, Illinois 61801, USA [2] Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Tsang
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300200, China.
authors.forename: Jiaxi
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Molecular Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
authors.forename: Charles L
authors.initials: CL
authors.lastname: Cox
authors.affiliation: Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Cheng
authors.affiliation: 1] Department of Cell and Developmental Biology, South Goodwin Avenue, Urbana, Illinois 61801, USA [2] Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D004594:Electrophysiology; D006801:Humans; D060850:LIM-Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009046:Motor Neurons / Q000166:cytology* / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D060850:LIM-Homeodomain Proteins; D014157:Transcription Factors; C063843:insulin gene enhancer binding protein Isl-1