Oscillatory Control of Factors Determining Multipotency and Fate in Mouse Neural Progenitors
Oscillatory Control of Factors Determining Multipotency and Fate in Mouse Neural Progenitors
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DOI：
10.1126/science.1242366
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发表时间：
2013-12-06
期刊：
影响因子：
56.9
通讯作者：
Kageyama, Ryoichiro
中科院分区：
文献类型：
--
作者：
Imayoshi, Itaru;Isomura, Akihiro;Kageyama, Ryoichiro
碱性螺旋-环-螺旋转录因子Ascl 1/Mash 1、Hes 1和Olig 2分别调节神经元、星形胶质细胞和少突胶质细胞的命运选择。这些相同的因子由神经祖细胞共表达。在这里，我们发现，通过延时成像，这些因素是由小鼠神经祖细胞以振荡的方式表达。在每个分化谱系中，其中一个因素成为主导。我们使用光遗传学来控制Ascl 1的表达，发现尽管持续的Ascl 1表达促进神经元命运决定，但振荡的Ascl 1表达维持增殖的神经祖细胞。因此，多能状态与几个命运决定因子的振荡表达相关，而分化状态与单个因子的持续表达相关。
The basic helix-loop-helix transcription factors Ascl1/Mash1, Hes1, and Olig2 regulate fate choice of neurons, astrocytes, and oligodendrocytes, respectively. These same factors are coexpressed by neural progenitor cells. Here, we found by time-lapse imaging that these factors are expressed in an oscillatory manner by mouse neural progenitor cells. In each differentiation lineage, one of the factors becomes dominant. We used optogenetics to control expression of Ascl1 and found that, although sustained Ascl1 expression promotes neuronal fate determination, oscillatory Ascl1 expression maintains proliferating neural progenitor cells. Thus, the multipotent state correlates with oscillatory expression of several fate-determination factors, whereas the differentiated state correlates with sustained expression of a single factor.