Olig2-Regulated Lineage-Restricted Pathway Controls Replication Competence in Neural Stem Cells and Malignant Glioma

Keith L. Ligon, Emmanuelle Huillard, Shwetal Mehta, Santosh Kesari, Hongye Liu, John A. Alberta, Robert M. Bachoo, Michael Kane, David N. Louis, Ronald A. DePinho, David J. Anderson, Charles D. Stiles, David H. Rowitch

Research output: Contribution to journalArticlepeer-review

339 Scopus citations

Abstract

Recent studies have identified stem cells in brain cancer. However, their relationship to normal CNS progenitors, including dependence on common lineage-restricted pathways, is unclear. We observe expression of the CNS-restricted transcription factor, OLIG2, in human glioma stem and progenitor cells reminiscent of type C transit-amplifying cells in germinal zones of the adult brain. Olig2 function is required for proliferation of neural progenitors and for glioma formation in a genetically relevant murine model. Moreover, we show p21WAF1/CIP1, a tumor suppressor and inhibitor of stem cell proliferation, is directly repressed by OLIG2 in neural progenitors and gliomas. Our findings identify an Olig2-regulated lineage-restricted pathway critical for proliferation of normal and tumorigenic CNS stem cells.

Original languageEnglish (US)
Pages (from-to)503-517
Number of pages15
JournalNeuron
Volume53
Issue number4
DOIs
StatePublished - Feb 15 2007

Keywords

  • HUMDISEASE
  • MOLNEURO
  • STEMCELL

ASJC Scopus subject areas

  • Neuroscience(all)

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