Cell-cycle-independent transitions in temporal identity of mammalian neural progenitor cells

Mayumi Okamoto, Takaki Miyata, Daijiro Konno, Hiroki R. Ueda, Takeya Kasukawa, Mitsuhiro Hashimoto, Fumio Matsuzaki () and Ayano Kawaguchi ()
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Mayumi Okamoto: Nagoya University Graduate School of Medicine
Takaki Miyata: Nagoya University Graduate School of Medicine
Daijiro Konno: Laboratory for Cell Asymmetry, Center for Developmental Biology, RIKEN Kobe Institute
Hiroki R. Ueda: Laboratory for Systems Biology, Center for Developmental Biology, RIKEN Kobe Institute
Takeya Kasukawa: Functional Genomics Unit, Center for Developmental Biology, RIKEN Kobe Institute
Mitsuhiro Hashimoto: Nagoya University Graduate School of Medicine
Fumio Matsuzaki: Laboratory for Cell Asymmetry, Center for Developmental Biology, RIKEN Kobe Institute
Ayano Kawaguchi: Nagoya University Graduate School of Medicine

Nature Communications, 2016, vol. 7, issue 1, 1-16

Abstract: Abstract 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.

Date: 2016
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DOI: 10.1038/ncomms11349

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