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

被引:285
作者
Karumbayaram, Saravanan [1 ]
Novitch, Bennett G. [2 ,6 ]
Patterson, Michaela [5 ]
Umbach, Joy A. [3 ]
Richter, Laura [5 ]
Lindgren, Anne [5 ]
Conway, Anne E. [5 ]
Clark, Amander T. [5 ,6 ]
Goldman, Steve A. [9 ]
Plath, Kathrin [4 ,6 ]
Wiedau-Pazos, Martina [1 ]
Kornblum, Harley I. [3 ,6 ,7 ,8 ]
Lowry, William E. [5 ,6 ]
机构
[1] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA
[2] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA
[3] Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA
[4] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biol Chem, Los Angeles, CA 90095 USA
[5] Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA
[6] Univ Calif Los Angeles, Broad Stem Cell Ctr, Los Angeles, CA 90095 USA
[7] Univ Calif Los Angeles, Mental Retardat Res Ctr, Los Angeles, CA 90095 USA
[8] Univ Calif Los Angeles, Semel Inst, Los Angeles, CA 90095 USA
[9] Univ Rochester, Dept Neurol, Ctr Translat Neuromed, Rochester, NY USA
关键词
Embryonic stem cells; Neural differentiation; Neuron; Reprogramming; Pluripotent stem cell; POOL IDENTITY; MOTONEURONS; SPECIFICATION;
D O I
10.1002/stem.31
中图分类号
Q813 [细胞工程];
学科分类号
摘要
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
引用
收藏
页码:806 / 811
页数:6
相关论文
共 22 条
  • [1] Balice-Gordon RJ, 2000, ANN NEUROL, V47, P596, DOI 10.1002/1531-8249(200005)47:5<596::AID-ANA7>3.0.CO
  • [2] 2-I
  • [3] Early electrophysiological abnormalities in lumbar motoneurons in a transgenic mouse model of amyotrophic lateral sclerosis
    Bories, Cyril
    Amendola, Julien
    d'Incamps, Boris Lamotte
    Durand, Jacques
    [J]. EUROPEAN JOURNAL OF NEUROSCIENCE, 2007, 25 (02) : 451 - 459
  • [4] Vertebrate neurogenesis is counteracted by Sox1-3 activity
    Bylund, M
    Andersson, E
    Novitch, BG
    Muhr, J
    [J]. NATURE NEUROSCIENCE, 2003, 6 (11) : 1162 - 1168
  • [5] A Hox regulatory network establishes motor neuron pool identity and target-muscle connectivity
    Dasen, JS
    Tice, BC
    Brenner-Morton, S
    Jessell, TM
    [J]. CELL, 2005, 123 (03) : 477 - 491
  • [6] Motor neuron columnar fate imposed by sequential phases of Hox-c activity
    Dasen, JS
    Liu, JP
    Jessell, TM
    [J]. NATURE, 2003, 425 (6961) : 926 - 933
  • [7] Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons
    Dimos, John T.
    Rodolfa, Kit T.
    Niakan, Kathy K.
    Weisenthal, Laurin M.
    Mitsumoto, Hiroshi
    Chung, Wendy
    Croft, Gist F.
    Saphier, Genevieve
    Leibel, Rudy
    Goland, Robin
    Wichterle, Hynek
    Henderson, Christopher E.
    Eggan, Kevin
    [J]. SCIENCE, 2008, 321 (5893) : 1218 - 1221
  • [8] Induced pluripotent stem cells from a spinal muscular atrophy patient
    Ebert, Allison D.
    Yu, Junying
    Rose, Ferrill F., Jr.
    Mattis, Virginia B.
    Lorson, Christian L.
    Thomson, James A.
    Svendsen, Clive N.
    [J]. NATURE, 2009, 457 (7227) : 277 - U1
  • [9] Development of ionic currents underlying changes in action potential waveforms in rat spinal motoneurons
    Gao, BX
    Ziskind-Conhaim, L
    [J]. JOURNAL OF NEUROPHYSIOLOGY, 1998, 80 (06) : 3047 - 3061
  • [10] Early motor neuron pool identity and muscle nerve trajectory defined by postmitotic restrictions in Nkx6.1 activity
    Garcia, Natalia V. De Marco
    Jessell, Thomas M.
    [J]. NEURON, 2008, 57 (02) : 217 - 231