Deregulation of dorsoventral patterning by FGF confers trilineage differentiation capacity on CNS stem cells in vitro

Limor Gabay, Sally Lowell, Lee L Rubin, David J Anderson

Research output: Contribution to journalArticlepeer-review

Abstract

The CNS is thought to develop from self-renewing stem cells that generate neurons, astrocytes, and oligodendrocytes. Other data, however, have suggested that astrocytes and oligodendrocytes are generated from separate progenitor populations. To reconcile these observations, we have prospectively isolated progenitors that do or do not express Olig2, an oligodendrocyte bHLH determination factor. Both Olig2(-) and Olig2(+) progenitors can behave as tripotential CNS stem cells (CNS-SCs) in vitro. Growth in FGF-2 causes induction of Olig2 in the former population, permitting oligodendrocyte differentiation; extinction of Olig2 in the latter cells permits astrocyte differentiation. The induction of Olig2 by FGF-2 is mediated, in part, via endogenous Sonic Hedgehog. These data indicate that clonogenic competence to generate neurons, astrocytes, and oligodendrocytes reflects a deregulation of dorsoventral patterning during expansion in vitro, raising the question of whether such trifatent cells actually exist in vivo.
Original languageEnglish
Pages (from-to)485-99
Number of pages15
JournalNeuron
Volume40
Issue number3
Publication statusPublished - 2003

Keywords

  • Animals
  • Antigens
  • Astrocytes
  • Basic Helix-Loop-Helix Transcription Factors
  • Blotting, Northern
  • Body Patterning
  • Bromodeoxyuridine
  • Carbocyanines
  • Cell Aggregation
  • Cell Count
  • Cell Differentiation
  • Cells, Cultured
  • DNA-Binding Proteins
  • Dose-Response Relationship, Drug
  • Embryo, Mammalian
  • Enzyme Inhibitors
  • Epidermal Growth Factor
  • Epithelial Cells
  • Fibroblast Growth Factor 2
  • Flow Cytometry
  • Glial Fibrillary Acidic Protein
  • Green Fluorescent Proteins
  • Hedgehog Proteins
  • High Mobility Group Proteins
  • Homeodomain Proteins
  • Immunohistochemistry
  • Luminescent Proteins
  • Mice
  • Nerve Tissue Proteins
  • Neurons
  • O Antigens
  • Oligodendroglia
  • PAX7 Transcription Factor
  • Proteoglycans
  • RNA, Messenger
  • Rats
  • Receptor, Platelet-Derived Growth Factor alpha
  • Reverse Transcriptase Polymerase Chain Reaction
  • SOXE Transcription Factors
  • Spinal Cord
  • Stem Cells
  • Time Factors
  • Trans-Activators
  • Transcription Factors
  • Transfection
  • Tubulin
  • beta-Galactosidase

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