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

• Published in: Molecular and cellular neuroscience 2007-07, Vol.35 (3), p.424-435
• Main Authors: Pistollato, Francesca, Chen, Hui-Ling, Schwartz, Philip H., Basso, Giuseppe, Panchision, David M.
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Antigens, CD - metabolism; Astrocyte; Astrocytes - drug effects; Bone morphogenetic proteins; Bone Morphogenetic Proteins - genetics; Bone Morphogenetic Proteins - metabolism; Brain; CD133 antigen; 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; Oligodendrocyte; Oligodendroglia - drug effects; Oxygen; Oxygen - pharmacology; Stem Cells - drug effects; Stem Cells - physiology; Stem cells/Progenitor cells; Time Factors
• ISSN: 1044-7431; 1095-9327
• DOI: 10.1016/j.mcn.2007.04.003

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.