Neuron-Astroglia Cell Fate Decision in the Adult Mouse Hippocampal Neurogenic Niche Is Cell-Intrinsically Controlled by COUP-TFI In Vivo
Neuron-Astroglia Cell Fate Decision in the Adult Mouse Hippocampal Neurogenic Niche Is Cell-Intrinsically Controlled by COUP-TFI In Vivo
Blog Article
Summary: In the dentate gyrus (DG) of the mouse hippocampus, neurogenesis and astrogliogenesis persist throughout life.Adult-born neurons and here astrocytes originate from multipotent neural stem cells (NSCs) whose activity is tightly regulated within the neurogenic niche.However, the cell-intrinsic mechanisms controlling neuron-glia NSC fate choice are largely unknown.Here, we show COUP-TFI/NR2F1 expression in DG NSCs and its downregulation upon neuroinflammation.By using in vivo inducible knockout lines, a retroviral-based loss-of-function approach and genetic fate mapping, we demonstrate that COUP-TFI inactivation in adult NSCs and/or mitotic progenitors reduces neurogenesis and increases astrocyte production without depleting the NSC pool.
Moreover, forced COUP-TFI expression in adult NSCs/progenitors decreases DG astrogliogenesis and rescues the neuro-astrogliogenic imbalance under neuroinflammation.Thus, COUP-TFI is necessary and sufficient to promote neurogenesis by suppressing astrogliogenesis.Our data propose COUP-TFI as a central regulator of the neuron-astroglia cell fate g35 coupe fender decision and a key modulator during neuroinflammation in the adult hippocampus.: The adult hippocampal dentate gyrus contains multipotent neural stem cells (NSCs) and neuronal committed progenitors.Bonzano et al.
demonstrate that the nuclear receptor COUP-TFI cell-intrinsically drives NSCs/progenitors toward neurogenesis by repressing astrogliogenesis.Notably, COUP-TFI downregulation occurs in inflamed hippocampi, and its overexpression rescues the hippocampal neurogenesis-astrogliogenesis imbalance due to neuroinflammation.Keywords: adult neurogenesis, dentate gyrus, neuroinflammation, NR2F1, neural stem cells, neural progenitors, astrogliogenesis.