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Cell Rep. 2018 Jul 10;24(2):329-341. doi: 10.1016/j.celrep.2018.06.044.

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

Author information

1
Neuroscience Institute Cavalieri Ottolenghi (NICO), University of Turin, Orbassano 10043, Italy; Department of Life Sciences and Systems Biology, University of Turin, Turin 10123, Italy; Université Côte d'Azur (UCA) CNRS, Inserm, iBV, Nice 06108, France.
2
Neuroscience Institute Cavalieri Ottolenghi (NICO), University of Turin, Orbassano 10043, Italy; Department of Life Sciences and Systems Biology, University of Turin, Turin 10123, Italy.
3
Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch 67404, France; Inserm, U1258, Illkirch, France; CNRS, UMR 7104, Illkirch, France; Université de Strasbourg, Illkirch, France.
4
Department of Biomedicine, University of Basel, Basel 4031, Switzerland.
5
Université Côte d'Azur (UCA) CNRS, Inserm, iBV, Nice 06108, France. Electronic address: michele.studer@unice.fr.
6
Neuroscience Institute Cavalieri Ottolenghi (NICO), University of Turin, Orbassano 10043, Italy; Department of Life Sciences and Systems Biology, University of Turin, Turin 10123, Italy. Electronic address: silvia.demarchis@unito.it.

Abstract

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.

KEYWORDS:

NR2F1; adult neurogenesis; astrogliogenesis; dentate gyrus; neural progenitors; neural stem cells; neuroinflammation

PMID:
29996095
DOI:
10.1016/j.celrep.2018.06.044
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