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

Sara Bonzano (1, 2) , Isabella Crisci (1) , Anna Podlesny-Drabiniok (3) , Chiara Rolando (4) , Wojciech Krężel (3) , Michèle Studer (2) , Silvia de Marchis (1)

1 UNITO - Università degli studi di Torino = University of Turin
2 IBV - Institut de Biologie Valrose
3 IGBMC - Institut de génétique et biologie moléculaire et cellulaire
4 Unibas - Université de Bâle = University of Basel = Basel Universität

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.

Domaines: Neurobiologie

Sara Bonzano, Isabella Crisci, Anna Podlesny-Drabiniok, Chiara Rolando, Wojciech Krężel, et al.. Neuron-Astroglia Cell Fate Decision in the Adult Mouse Hippocampal Neurogenic Niche Is Cell-Intrinsically Controlled by COUP-TFI In Vivo. Cell Reports, 2018, 24 (2), pp.329-341. ⟨10.1016/j.celrep.2018.06.044⟩. ⟨hal-03671898⟩