Premium
Relief of hypoxia by angiogenesis promotes neural stem cell differentiation by targeting glycolysis
Author(s) -
Lange Christian,
Turrero Garcia Miguel,
Decimo Ilaria,
Bifari Francesco,
Eelen Guy,
Quaegebeur Annelies,
Boon Ruben,
Zhao Hui,
Boeckx Bram,
Chang Junlei,
Wu Christine,
Le Noble Ferdinand,
Lambrechts Diether,
Dewerchin Mieke,
Kuo Calvin J,
Huttner Wieland B,
Carmeliet Peter
Publication year - 2016
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201592372
Subject(s) - biology , angiogenesis , hypoxia (environmental) , glycolysis , microbiology and biotechnology , neural stem cell , stem cell , cellular differentiation , cancer research , genetics , biochemistry , metabolism , gene , oxygen , chemistry , organic chemistry
Blood vessels are part of the stem cell niche in the developing cerebral cortex, but their in vivo role in controlling the expansion and differentiation of neural stem cells ( NSC s) in development has not been studied. Here, we report that relief of hypoxia in the developing cerebral cortex by ingrowth of blood vessels temporo‐spatially coincided with NSC differentiation. Selective perturbation of brain angiogenesis in vessel‐specific Gpr124 null embryos, which prevented the relief from hypoxia, increased NSC expansion at the expense of differentiation. Conversely, exposure to increased oxygen levels rescued NSC differentiation in Gpr124 null embryos and increased it further in WT embryos, suggesting that niche blood vessels regulate NSC differentiation at least in part by providing oxygen. Consistent herewith, hypoxia‐inducible factor ( HIF )‐1α levels controlled the switch of NSC expansion to differentiation. Finally, we provide evidence that high glycolytic activity of NSC s is required to prevent their precocious differentiation in vivo . Thus, blood vessel function is required for efficient NSC differentiation in the developing cerebral cortex by providing oxygen and possibly regulating NSC metabolism.