Single-cell gene profiling defines differential progenitor subclasses in mammalian neurogenesis

Ayano Kawaguchi, Tomoko Ikawa, Takeya Kasukawa, Hiroki R. Ueda, Kazuki Kurimoto, Mitinori Saitou, Fumio Matsuzaki

Research output: Contribution to journalArticlepeer-review

158 Citations (Scopus)

Abstract

Cellular diversity of the brain is largely attributed to the spatial and temporal heterogeneity of progenitor cells. In mammalian cerebral development, it has been difficult to determine how heterogeneous the neural progenitor cells are, owing to dynamic changes in their nuclear position and gene expression. To address this issue, we systematically analyzed the cDNA profiles of a large number of single progenitor cells at the mid-embryonic stage in mouse. By cluster analysis and in situ hybridization, we have identified a set of genes that distinguishes between the apical and basal progenitors. Despite their relatively homogeneous global gene expression profiles, the apical progenitors exhibit highly variable expression patterns of Notch signaling components, raising the possibility that this causes the heterogeneous division patterns of these cells. Furthermore, we successfully captured the nascent state of basal progenitor cells. These cells are generated shortly after birth from the division of the apical progenitors, and show strong expression of the major Notch ligand delta-like 1, which soon fades away as the cells migrate in the ventricular zone. We also demonstrated that attenuation of Notch signals immediately induces differentiation of apical progenitors into nascent basal progenitors. Thus, a Notch-dependent feedback loop is likely to be in operation to maintain both progenitor populations.

Original languageEnglish
Pages (from-to)3113-3124
Number of pages12
JournalDevelopment
Volume135
Issue number18
DOIs
Publication statusPublished - 2008
Externally publishedYes

Keywords

  • Cortical development
  • Neural progenitors
  • Neurogenesis
  • Notch signaling
  • Single-cell cDNA

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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