Howard Hughes Medical Institute, Janelia Research Campus, 19700 Helix Drive, Ashburn, VA, USA.
Howard Hughes Medical Institute, Janelia Research Campus, 19700 Helix Drive, Ashburn, VA, USA. Departments of Bioengineering, Electrical Engineering, and Computer Science, and Biophysics Graduate Program, University of California Berkeley, 408C Stanley Hall, Berkeley, CA, USA.
Science. 2015 Oct 16;350(6258):317-20. doi: 10.1126/science.aad1886.
Neural stem cells show age-dependent developmental potentials, as evidenced by their production of distinct neuron types at different developmental times. Drosophila neuroblasts produce long, stereotyped lineages of neurons. We searched for factors that could regulate neural temporal fate by RNA-sequencing lineage-specific neuroblasts at various developmental times. We found that two RNA-binding proteins, IGF-II mRNA-binding protein (Imp) and Syncrip (Syp), display opposing high-to-low and low-to-high temporal gradients with lineage-specific temporal dynamics. Imp and Syp promote early and late fates, respectively, in both a slowly progressing and a rapidly changing lineage. Imp and Syp control neuronal fates in the mushroom body lineages by regulating the temporal transcription factor Chinmo translation. Together, the opposing Imp/Syp gradients encode stem cell age, specifying multiple cell fates within a lineage.
神经干细胞表现出与年龄相关的发育潜能，这可以从它们在不同发育时间产生不同类型的神经元中得到证明。果蝇神经母细胞产生长而刻板的神经元谱系。我们通过 RNA 测序在不同的发育时间对谱系特异性神经母细胞进行搜索，寻找可以调节神经时间命运的因素。我们发现两种 RNA 结合蛋白，胰岛素样生长因子 II mRNA 结合蛋白（Imp）和 Syncrip（Syp），表现出与谱系特异性时间动态相反的高到低和低到高的时间梯度。Imp 和 Syp 分别在一个进展缓慢和变化迅速的谱系中促进早期和晚期命运。Imp 和 Syp 通过调节时间转录因子 Chinmo 的翻译来控制蘑菇体谱系中的神经元命运。相反的 Imp/Syp 梯度共同编码干细胞年龄，在一个谱系内指定多个细胞命运。
