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

被引:286
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
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