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Publication : Neuron-Astroglia Cell Fate Decision in the Adult Mouse Hippocampal Neurogenic Niche Is Cell-Intrinsically Controlled by COUP-TFI In Vivo.

First Author  Bonzano S Year  2018
Journal  Cell Rep Volume  24
Issue  2 Pages  329-341
PubMed ID  29996095 Mgi Jnum  J:270783
Mgi Id  MGI:6278717 Doi  10.1016/j.celrep.2018.06.044
Citation  Bonzano S, et al. (2018) Neuron-Astroglia Cell Fate Decision in the Adult Mouse Hippocampal Neurogenic Niche Is Cell-Intrinsically Controlled by COUP-TFI In Vivo. Cell Rep 24(2):329-341
abstractText  In the dentate gyrus (DG) of the mouse hippocampus, neurogenesis and astrogliogenesis persist throughout life. Adult-born neurons and 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 decision and a key modulator during neuroinflammation in the adult hippocampus.
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