Okamoto Mayumi, Miyata Takaki, Konno Daijiro, Ueda Hiroki R, Kasukawa Takeya, Hashimoto Mitsuhiro, Matsuzaki Fumio, Kawaguchi Ayano
Department of Anatomy and Cell Biology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya, Aichi 466-8550, Japan.
Laboratory for Cell Asymmetry, Center for Developmental Biology, RIKEN Kobe Institute, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
Nat Commun. 2016 Apr 20;7:11349. doi: 10.1038/ncomms11349.
During cerebral development, many types of neurons are sequentially generated by self-renewing progenitor cells called apical progenitors (APs). Temporal changes in AP identity are thought to be responsible for neuronal diversity; however, the mechanisms underlying such changes remain largely unknown. Here we perform single-cell transcriptome analysis of individual progenitors at different developmental stages, and identify a subset of genes whose expression changes over time but is independent of differentiation status. Surprisingly, the pattern of changes in the expression of such temporal-axis genes in APs is unaffected by cell-cycle arrest. Consistent with this, transient cell-cycle arrest of APs in vivo does not prevent descendant neurons from acquiring their correct laminar fates. Analysis of cultured APs reveals that transitions in AP gene expression are driven by both cell-intrinsic and -extrinsic mechanisms. These results suggest that the timing mechanisms controlling AP temporal identity function independently of cell-cycle progression and Notch activation mode.
在大脑发育过程中，许多类型的神经元由称为顶端祖细胞（APs）的自我更新祖细胞依次产生。AP身份的时间变化被认为是神经元多样性的原因；然而，这种变化背后的机制在很大程度上仍然未知。在这里，我们对不同发育阶段的单个祖细胞进行单细胞转录组分析，并鉴定出一组基因，其表达随时间变化但与分化状态无关。令人惊讶的是，APs中此类时间轴基因表达的变化模式不受细胞周期停滞的影响。与此一致，体内APs的短暂细胞周期停滞并不能阻止后代神经元获得其正确的层状命运。对培养的APs的分析表明，AP基因表达的转变是由细胞内在和外在机制共同驱动的。这些结果表明，控制AP时间身份的时间机制独立于细胞周期进程和Notch激活模式发挥作用。
