Abstract：
Neural stem cells (NSCs) differentiate into neuron-fated intermediate progenitor cells (IPCs) via cell division. Although differentiation from NSCs to IPCs is a discrete process, recent transcriptome analyses identified a continuous transcriptional trajectory during this process, raising the question of how to reconcile these contradictory observations. In mouse NSCs, Hes1 expression oscillates, regulating the oscillatory expression of the proneural gene Neurog2, while Hes1 expression disappears in IPCs. Thus, the transition from Hes1 oscillation to suppression is involved in the differentiation of NSCs to IPCs. Here, we found that Neurog2 oscillations induce the accumulation of Tbr2, which suppresses Hes1 expression, generating an IPC-like gene expression state in NSCs. In the absence of Tbr2, Hes1 expression is up-regulated, decreasing the formation of IPCs. These results indicate that the Neurog2-Tbr2 axis forms a continuous transcriptional trajectory to an IPC-like neurogenic state in NSCs, which then differentiate into IPCs via cell division.
摘要：
神经干细胞（NSC）通过细胞分裂分化为神经元命运的中间祖细胞（IPC）。虽然从NSC到IPC的分化是一个离散的过程，最近的转录组分析确定了在这个过程中连续的转录轨迹，提出了如何调和这些相互矛盾的观察的问题。在小鼠NSC中，Hes1表达振荡，调节前神经基因Neurog2的振荡表达，而IPC中Hes1的表达消失。因此，从Hes1振荡到抑制的转变参与了神经干细胞向IPC的分化。这里,我们发现Neurog2振荡诱导Tbr2的积累，抑制Hes1表达，在NSC中产生IPC样基因表达状态。在没有Tbr2的情况下，Hes1表达上调，减少IPC的形成。这些结果表明，Neurog2-Tbr2轴在NSC中形成了一个连续的转录轨迹到IPC样神经发生状态，然后通过细胞分裂分化为IPC。
