Oxygen tension controls the expansion of human CNS precursors and the generation of astrocytes and oligodendrocytes

Mol Cell Neurosci. 2007 Jul;35(3):424-35. doi: 10.1016/j.mcn.2007.04.003. Epub 2007 Apr 12.


Human neural precursor proliferation and potency is limited by senescence and loss of oligodendrocyte potential. We found that in vitro expansion of human postnatal brain CD133(+) nestin(+) precursors is enhanced at 5% oxygen, while raising oxygen tension to 20% depletes precursors and promotes astrocyte differentiation even in the presence of mitogens. Higher cell densities yielded more astrocytes regardless of oxygen tension. This was reversed by noggin at 5%, but not 20%, oxygen due to a novel repressive effect of low oxygen on bone morphogenetic protein (BMP) signaling. When induced to differentiate by mitogen withdrawal, 5% oxygen-expanded precursors generated 17-fold more oligodendrocytes than cells expanded in 20% oxygen. When precursors were expanded at 5% oxygen and then differentiated at 20% oxygen, oligodendrocyte maturation was further enhanced 2.5-fold. These results indicate that dynamic control of oxygen tension regulates different steps in fate and maturation and may be crucial for treating neurodegenerative diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Antigens, CD / metabolism
  • Astrocytes / drug effects*
  • Bone Morphogenetic Proteins / genetics
  • Bone Morphogenetic Proteins / metabolism
  • Cell Count
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Central Nervous System / cytology*
  • Central Nervous System / embryology
  • Central Nervous System / growth & development
  • Dose-Response Relationship, Drug
  • Fetus
  • Flow Cytometry / methods
  • Humans
  • Infant, Newborn
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Oligodendroglia / drug effects*
  • Oxygen / pharmacology*
  • Stem Cells / drug effects*
  • Stem Cells / physiology
  • Time Factors


  • Antigens, CD
  • Bone Morphogenetic Proteins
  • Nerve Tissue Proteins
  • Oxygen