Cell cycle-independent temporal identity transitions in cortical progenitor cells as revealed by single cell transcriptome analysis

During cerebral development, a variety of neurons are sequentially generated by self-renewing progenitor cells, apical progenitors (APs). A temporal change in AP identity is thought to produce a diversity of progeny neurons, while underlying mechanisms are largely unknown. Here we performed single cell genome-wide transcriptome profiling of APs at different neurogenic stages, and identified a set of genes that are temporally expressed in APs in a manner independent of differentiation state. Surprisingly, the temporal pattern of such AP gene expression was not affected by arresting cell cycling. Consistently, a transient cell cycle arrest of APs in vivo did not prevent descendant neurons to acquire their correct laminar fates. in vitro cell culture of APs revealed that transitions in AP gene expression involved in both cell-autonomous and non-autonomous mechanisms. These results suggest that timers controlling AP temporal identity run independently of cell cycle progression and Notch activation mode.

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Okamoto M, Miyata T, Konno D, Ueda HR, Kasukawa T, Hashimoto M, Matsuzaki F, Kawaguchi A