title: Oxygen tension controls the expansion of human CNS precursors and the generation of astrocytes and oligodendrocytes.
abstract: 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.
authors.affiliation: Center for Neuroscience Research, Children's Research Institute, Children's National Medical Center, 5th Floor, Suite 5340, 111 Michigan Avenue, N.W., Washington, DC 20010, USA.
authors.forename: Francesca
authors.initials: F
authors.lastname: Pistollato
authors.forename: Hui-Ling
authors.initials: HL
authors.lastname: Chen
authors.forename: Philip H
authors.initials: PH
authors.lastname: Schwartz
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Basso
authors.forename: David M
authors.initials: DM
authors.lastname: Panchision
mesh_terms: D000704:Analysis of Variance; D015703:Antigens, CD / Q000378:metabolism; D001253:Astrocytes / Q000187:drug effects*; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology* / Q000196:embryology / Q000254:growth & development; D004305:Dose-Response Relationship, Drug; D005333:Fetus; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D007231:Infant, Newborn; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009836:Oligodendroglia / Q000187:drug effects*; D010100:Oxygen / Q000494:pharmacology*; D013234:Stem Cells / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors
chemical_list: D015703:Antigens, CD; D019485:Bone Morphogenetic Proteins; D009419:Nerve Tissue Proteins; D010100:Oxygen