Cell-cycle-independent transitions in temporal identity of mammalian neural progenitor cells.
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.
Department of Anatomy and Cell Biology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya, Aichi 466-8550, Japan.
Mayumi
M
Okamoto
Department of Anatomy and Cell Biology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya, Aichi 466-8550, Japan.
Takaki
T
Miyata
Laboratory for Cell Asymmetry, Center for Developmental Biology, RIKEN Kobe Institute, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
Daijiro
D
Konno
Laboratory for Systems Biology, Center for Developmental Biology, RIKEN Kobe Institute, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.|Functional Genomics Unit, Center for Developmental Biology, RIKEN Kobe Institute, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
Hiroki R
HR
Ueda
Functional Genomics Unit, Center for Developmental Biology, RIKEN Kobe Institute, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.|Large Scale Data Managing Unit, Center for Life Science Technologies, RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama City, Kanagawa 230-0045, Japan.
Takeya
T
Kasukawa
Department of Anatomy and Cell Biology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya, Aichi 466-8550, Japan.|Department of Anatomy, Fukushima Medical University, 1 Hikarigaoka, Fukushima 960-1295, Japan.
Mitsuhiro
M
Hashimoto
Laboratory for Cell Asymmetry, Center for Developmental Biology, RIKEN Kobe Institute, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
Fumio
F
Matsuzaki
Department of Anatomy and Cell Biology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya, Aichi 466-8550, Japan.
Ayano
A
Kawaguchi
D000818:Animals; D059447:Cell Cycle Checkpoints / Q000235:genetics; D002454:Cell Differentiation; D019070:Cell Lineage / Q000235:genetics*; D002540:Cerebral Cortex / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D004622:Embryo, Mammalian; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D054778:NM23 Nucleoside Diphosphate Kinases / Q000235:genetics / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D055495:Neurogenesis / Q000235:genetics*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D059010:Single-Cell Analysis; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
C491198:Eomes protein, mouse; D008565:Membrane Proteins; D054778:NM23 Nucleoside Diphosphate Kinases; C497762:Notch1 protein, mouse; D051881:Receptor, Notch1; D020825:T-Box Domain Proteins; C485951:Ttyh1 protein, mouse; C517941:Nme2 protein, mouse