Embryonic Stem Cells/Induced Pluripotent Stem Cells

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Directed Differentiation of Human-Induced Pluripotent Stem Cells Generates Active Motor Neurons†‡

  1. Saravanan Karumbayaram1,
  2. Bennett G. Novitch2,3,
  3. Michaela Patterson4,
  4. Joy A. Umbach5,
  5. Laura Richter4,
  6. Anne Lindgren4,
  7. Anne E. Conway4,
  8. Amander T. Clark3,4,
  9. Steve A. Goldman6,
  10. Kathrin Plath3,7,
  11. Martina Wiedau-pazos1,
  12. Harley I. Kornblum3,5,8,
  13. William E. Lowry3,4,§,*

Article first published online: 23 FEB 2009

DOI: 10.1002/stem.31

Issue

STEM CELLS

STEM CELLS

Volume 27, Issue 4, pages 806–811, April 2009

Additional Information

How to Cite

Karumbayaram, S., Novitch, B. G., Patterson, M., Umbach, J. A., Richter, L., Lindgren, A., Conway, A. E., Clark, A. T., Goldman, S. A., Plath, K., Wiedau-pazos, M., Kornblum, H. I. and Lowry, W. E. (2009), Directed Differentiation of Human-Induced Pluripotent Stem Cells Generates Active Motor Neurons. STEM CELLS, 27: 806–811. doi: 10.1002/stem.31

Author Information

  1. 1

    Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA

  2. 2

    Department of Neurobiology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA

  3. 3

    Broad Stem Cell Center, UCLA, Los Angeles, California, USA

  4. 4

    Department of Molecular, Cell and Developmental Biology, UCLA, Los Angeles, California, USA

  5. 5

    Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA

  6. 6

    Center for Translational Neuromedicine, Department of Neurology, University of Rochester, Rochester, New York, USA

  7. 7

    Department of Biological Chemistry, David Geffen School of Medicine at UCLA, Los Angeles, California, USA

  8. 8

    The Semel Institute and the Mental Retardation Research Center at UCLA, Los Angeles, California, USA

  1. §

    Telephone: 310-794-5175; Fax: 310-794-9323

*621 Charles Young Drive South, Mail Box 160606, Los Angeles, CA 90095

  1. †

    Author contributions: S.K.: conception and design, collection and assembly of data, data analysis and interpretation, manuscript writing, final approval of manuscript; B.N.: conception and design, collection and assembly of data, data analysis and interpretation, manuscript writing, final approval of manuscript, financial support; M.P.: collection and assembly of data, data analysis and interpretation; J.U.: conception and design, collection and assembly of data, data analysis and interpretation, manuscript writing, final approval of manuscript; L.R.: technical support, provision of study material; A.L.: collection and assembly of data; A.C.: collection and assembly of data; A.C.: collection and assembly of data, financial support; S.A.G.: data analysis and interpretation, manuscript writing, final approval of manuscript; K.P.: data analysis and interpretation, manuscript writing, final approval of manuscript; M.W.-P.: conception and design, data analysis and interpretation, manuscript writing, final approval of manuscript, financial support; H.I.K.: conception and design, data analysis and interpretation, manuscript writing, final approval of manuscript; W.E.L.: conception and design, data analysis and interpretation, manuscript writing, final approval of manuscript, and financial support. S.K., B.G.N., M.P. contributed equally to this work. B.G.N., M.W.P., H.I.K., and W.E.L. contributed equally to this work.

  2. ‡

    First published online in STEM CELLSExpress February 23, 2009.

Publication History

  1. Issue published online: 6 APR 2009
  2. Article first published online: 23 FEB 2009
  3. Accepted manuscript online: 23 FEB 2009 12:00AM EST
  4. Manuscript Accepted: 4 FEB 2009
  5. Manuscript Received: 4 AUG 2008

Funded by

  • CIRM. Grant Number: RS1-00259-1

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Keywords:

  • Embryonic stem cells;
  • Neural differentiation;
  • Neuron;
  • Reprogramming;
  • Pluripotent stem cell

Abstract

The potential for directed differentiation of human-induced pluripotent stem (iPS) cells to functional postmitotic neuronal phenotypes is unknown. Following methods shown to be effective at generating motor neurons from human embryonic stem cells (hESCs), we found that once specified to a neural lineage, human iPS cells could be differentiated to form motor neurons with a similar efficiency as hESCs. Human iPS-derived cells appeared to follow a normal developmental progression associated with motor neuron formation and possessed prototypical electrophysiological properties. This is the first demonstration that human iPS-derived cells are able to generate electrically active motor neurons. These findings demonstrate the feasibility of using iPS-derived motor neuron progenitors and motor neurons in regenerative medicine applications and in vitro modeling of motor neuron diseases. STEM CELLS 2009;27:806–811

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