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High-efficiency motor neuron differentiation from human pluripotent stem cells and the function of Islet-1

Author

Listed:
  • Qiuhao Qu

    (Department of Cell and Developmental Biology
    Institute for Genomic Biology, University of Illinois at Urbana-Champaign)

  • Dong Li

    (Department of Cell and Developmental Biology
    Institute for Genomic Biology, University of Illinois at Urbana-Champaign)

  • Kathleen R. Louis

    (University of Illinois at Urbana-Champaign)

  • Xiangzhen Li

    (Key Laboratory of Environmental and Applied Microbiology, Chengdu Institute of Biology, Chinese Academy of Sciences
    Environmental Microbiology Key Laboratory of Sichuan Province, Chengdu Institute of Biology, Chinese Academy of Sciences)

  • Hong Yang

    (Department of Cell and Developmental Biology
    Institute for Genomic Biology, University of Illinois at Urbana-Champaign)

  • Qinyu Sun

    (Department of Cell and Developmental Biology
    Institute for Genomic Biology, University of Illinois at Urbana-Champaign)

  • Shane R. Crandall

    (University of Illinois at Urbana-Champaign)

  • Stephanie Tsang

    (Department of Cell and Developmental Biology
    Institute for Genomic Biology, University of Illinois at Urbana-Champaign)

  • Jiaxi Zhou

    (State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Charles L. Cox

    (University of Illinois at Urbana-Champaign)

  • Jianjun Cheng

    (University of Illinois at Urbana-Champaign)

  • Fei Wang

    (Department of Cell and Developmental Biology
    Institute for Genomic Biology, University of Illinois at Urbana-Champaign)

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.

Suggested Citation

  • Qiuhao Qu & Dong Li & Kathleen R. Louis & Xiangzhen Li & Hong Yang & Qinyu Sun & Shane R. Crandall & Stephanie Tsang & Jiaxi Zhou & Charles L. Cox & Jianjun Cheng & Fei Wang, 2014. "High-efficiency motor neuron differentiation from human pluripotent stem cells and the function of Islet-1," Nature Communications, Nature, vol. 5(1), pages 1-13, May.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4449
    DOI: 10.1038/ncomms4449
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