title: Olig2-regulated lineage-restricted pathway controls replication competence in neural stem cells and malignant glioma.
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 p21(WAF1/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.
authors.affiliation: Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA.
authors.forename: Keith L
authors.initials: KL
authors.lastname: Ligon
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Huillard
authors.forename: Shwetal
authors.initials: S
authors.lastname: Mehta
authors.forename: Santosh
authors.initials: S
authors.lastname: Kesari
authors.forename: Hongye
authors.initials: H
authors.lastname: Liu
authors.forename: John A
authors.initials: JA
authors.lastname: Alberta
authors.forename: Robert M
authors.initials: RM
authors.lastname: Bachoo
authors.forename: Michael
authors.initials: M
authors.lastname: Kane
authors.forename: David N
authors.initials: DN
authors.lastname: Louis
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Depinho
authors.forename: David J
authors.initials: DJ
authors.lastname: Anderson
authors.forename: Charles D
authors.initials: CD
authors.lastname: Stiles
authors.forename: David H
authors.initials: DH
authors.lastname: Rowitch
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000172:deficiency / Q000378:metabolism*; D001932:Brain Neoplasms / Q000473:pathology*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation / Q000379:methods; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000172:deficiency; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D004622:Embryo, Mammalian; D005434:Flow Cytometry; D005910:Glioma / Q000473:pathology*; D049452:Green Fluorescent Proteins / Q000096:biosynthesis; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000378:metabolism*; D009474:Neurons / Q000502:physiology*; D000076104:Oligodendrocyte Transcription Factor 2; D013234:Stem Cells / Q000502:physiology*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D001973:Bromodeoxyuridine; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D049452:Green Fluorescent Proteins; D008156:Luciferases; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; C493956:CDKN1A protein, human; C512773:Olig2 protein, mouse