Global analysis of gene expression in neural progenitors reveals specific cell-cycle, signaling, and metabolic networks

Stanislav L. Karsten, Lili C. Kudo, Robert Jackson, Chiara Sabatti, Harley I. Kornblum, Daniel H. Geschwind

Research output: Contribution to journalArticlepeer-review

107 Scopus citations

Abstract

The genetic programs underlying neural stem cell (NSC) proliferation and pluripotentiality have only been partially elucidated. We compared the gene expression profile of proliferating neural stem cell cultures (NS) with cultures differentiated for 24 h (DC) to identify functionally coordinated alterations in gene expression associated with neural progenitor proliferation. The majority of differentially expressed genes (65%) were upregulated in NS relative to DC. Microarray analysis of this in vitro system was followed by high throughput screening in situ hybridization to identify genes enriched in the germinal neuroepithelium, so as to distinguish those expressed in neural progenitors from those expressed in more differentiated cells in vivo. NS cultures were characterized by the coordinate upregulation of genes involved in cell cycle progression, DNA synthesis, and metabolism, not simply related to general features of cell proliferation, since many of the genes identified were highly enriched in the CNS ventricular zones and not widely expressed in other proliferating tissues. Components of specific metabolic and signal transduction pathways, and several transcription factors, including Sox3, FoxM1, and PTTG1, were also enriched in neural progenitor cultures. We propose a putative network of gene expression linking cell cycle control to cell fate pathways, providing a framework for further investigations of neural stem cell proliferation and differentiation.

Original languageEnglish
Pages (from-to)165-182
Number of pages18
JournalDevelopmental Biology
Volume261
Issue number1
DOIs
StatePublished - 1 Sep 2003
Externally publishedYes

Keywords

  • Cell fate
  • Microarray analysis
  • Neural stem cell
  • Neurogenesis
  • Regulatory network

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