Oxygen Levels Regulate the Development of Human Cortical Radial Glia Cells.
Cereb Cortex
; 27(7): 3736-3751, 2017 07 01.
Article
em En
| MEDLINE
| ID: mdl-27600849
ABSTRACT
The oxygen (O2) concentration is a vital parameter for controlling the survival, proliferation, and differentiation of neural stem cells. A prenatal reduction of O2 levels (hypoxia) often leads to cognitive and behavioral defects, attributable to altered neural development. In this study, we analyzed the effects of O2 levels on human cortical progenitors, the radial glia cells (RGCs), during active neurogenesis, corresponding to the second trimester of gestation. Small changes in O2 levels profoundly affected RGC survival, proliferation, and differentiation. Physiological hypoxia (3% O2) promoted neurogenesis, whereas anoxia (<1% O2) and severe hypoxia (1% O2) arrested the differentiation of human RGCs, mainly by altering the generation of glutamatergic neurons. The in vitro activation of Wnt-ß-catenin signaling rescued the proliferation and neuronal differentiation of RGCs subjected to anoxia. Pathologic hypoxia (≤1% O2) also exerted negative effects on gliogenesis, by decreasing the number of O4+ preoligodendrocytes and increasing the number of reactive astrocytes derived from cortical RGCs. O2-dependent alterations in glutamatergic neurogenesis and oligodendrogenesis can lead to significant changes in cortical circuitry formation. A better understanding of the cellular effects caused by changes in O2 levels during human cortical development is essential to elucidating the etiology of numerous neurodevelopmental disorders.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Oxigênio
/
Hipóxia Celular
/
Córtex Cerebral
/
Regulação da Expressão Gênica no Desenvolvimento
/
Células-Tronco Neurais
/
Células Ependimogliais
Limite:
Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article