title: Cortical glial fibrillary acidic protein-positive cells generate neurons after perinatal hypoxic injury.
abstract: Glial fibrillary acidic protein-positive (GFAP(+)) cells give rise to new neurons in the neurogenic niches; whether they are able to generate neurons in the cortical parenchyma is not known. Here, we use genetic fate mapping to examine the progeny of GFAP(+) cells after postnatal hypoxia, a model for the brain injury observed in premature children. After hypoxia, immature cortical astroglia underwent a shift toward neuronal fate and generated cortical excitatory neurons that appeared synaptically integrated into the circuitry. Fate-mapped cortical GFAP(+) cells derived ex vivo from hypoxic, but not normoxic, mice were able to form pluripotent, long-term self-renewing neurospheres. Similarly, exposure to low oxygen conditions in vitro induced stem-cell-like potential in immature cortical GFAP(+) cells. Our data support the conclusion that hypoxia promotes pluripotency in GFAP(+) cells in the cortical parenchyma. Such plasticity possibly explains the cognitive recovery found in some preterm children.
authors.affiliation: Child Study Center, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
authors.forename: Baoyuan
authors.initials: B
authors.lastname: Bi
authors.forename: Natalina
authors.initials: N
authors.lastname: Salmaso
authors.forename: Mila
authors.initials: M
authors.lastname: Komitova
authors.forename: Maria V
authors.initials: MV
authors.lastname: Simonini
authors.forename: John
authors.initials: J
authors.lastname: Silbereis
authors.forename: Elise
authors.initials: E
authors.lastname: Cheng
authors.forename: Janice
authors.initials: J
authors.lastname: Kim
authors.forename: Suzannah
authors.initials: S
authors.lastname: Luft
authors.forename: Laura R
authors.initials: LR
authors.lastname: Ment
authors.forename: Tamas L
authors.initials: TL
authors.lastname: Horvath
authors.forename: Michael L
authors.initials: ML
authors.lastname: Schwartz
authors.forename: Flora M
authors.initials: FM
authors.lastname: Vaccarino
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D002478:Cells, Cultured; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism*; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism* / Q000473:pathology*; D010100:Oxygen / Q000378:metabolism*
chemical_list: D005904:Glial Fibrillary Acidic Protein; D010100:Oxygen