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

• DOI: 10.1016/j.celrep.2018.06.044
• Publication Date: 2018-07-11T18:11:11Z
• Authors: Sara Bonzano; Isabella Crisci; Anna Podlesny-Dra...; Chiara Rolando; Wojciech Krezel; Michèle Studer; Silvia De Marchis
• Keywords: Cell fate determination; Interneuron

In the dentate gyrus (DG) of mouse hippocampus, neurogenesis and astrogliogenesis persist throughout life. Adult-born neurons astrocytes originate from multipotent neural stem cells (NSCs) whose activity is tightly regulated within neurogenic niche. However, cell-intrinsic mechanisms controlling neuron-glia NSC fate choice are largely unknown. Here, we show COUP-TFI/NR2F1 expression in DG NSCs its downregulation upon neuroinflammation. By using vivo inducible knockout lines, a retroviral-based loss-of-function approach genetic mapping, demonstrate that COUP-TFI inactivation adult and/or mitotic progenitors reduces increases astrocyte production without depleting pool. Moreover, forced NSCs/progenitors decreases rescues neuro-astrogliogenic imbalance under Thus, necessary sufficient to promote by suppressing astrogliogenesis. Our data propose as central regulator neuron-astroglia cell decision key modulator during neuroinflammation hippocampus.