Wichterle Hynek, Lieberam Ivo, Porter Jeffery A, Jessell Thomas M
Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.
Cell. 2002 Aug 9;110(3):385-97. doi: 10.1016/s0092-8674(02)00835-8.
Inductive signals and transcription factors involved in motor neuron generation have been identified, raising the question of whether these developmental insights can be used to direct stem cells to a motor neuron fate. We show that developmentally relevant signaling factors can induce mouse embryonic stem (ES) cells to differentiate into spinal progenitor cells, and subsequently into motor neurons, through a pathway recapitulating that used in vivo. ES cell-derived motor neurons can populate the embryonic spinal cord, extend axons, and form synapses with target muscles. Thus, inductive signals involved in normal pathways of neurogenesis can direct ES cells to form specific classes of CNS neurons.
参与运动神经元生成的诱导信号和转录因子已被确定,这就提出了一个问题,即这些发育方面的见解是否可用于引导干细胞分化为运动神经元。我们发现,与发育相关的信号因子可通过一条重现体内过程的途径,诱导小鼠胚胎干细胞分化为脊髓祖细胞,随后再分化为运动神经元。胚胎干细胞衍生的运动神经元能够迁移至胚胎脊髓、延伸轴突并与靶肌肉形成突触。因此,神经发生正常途径中涉及的诱导信号能够引导胚胎干细胞形成特定类型的中枢神经系统神经元。