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Notch2 Signaling Regulates Id4 and Cell Cycle Genes to Maintain Neural Stem Cell Quiescence in the Adult Hippocampus

60 Pages Posted: 25 Jul 2018 Sneak Peek Status: Review Complete

See all articles by Runrui Zhang

Runrui Zhang

University of Basel - Embryology and Stem Cell Biology Lab

Marcelo Boareto

Swiss Institute of Bioinformatics (SIB)

Anna Engler

University of Basel - Embryology and Stem Cell Biology Lab

Angeliki Louvi

Yale University - Department of Neuroscience

Claudio Giachino

University Hospital Center Schleswig Holstein - Department of Neurosurgery

Dagmar Iber

Swiss Institute of Bioinformatics (SIB)

Verdon Taylor

University of Basel - Department of Biomedicine

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Abstract

Neural stem cells (NSCs) in the adult hippocampal dentate gyrus (DG) can be quiescent or proliferative, but how they are maintained is largely unknown. With age DG NSCs become increasingly dormant, which impinges on neuron generation. We addressed how NSC activity is controlled and found that Notch2 promotes quiescence by regulating their transition to the activated state. Notch2-ablation induces cell cycle genes and markers of active NSCs. Conversely, quiescent NSC-associated genes, including Id4, are down regulated after Notch2 deletion. We found that Notch2 binds the Id4 promoter and positively regulates transcription. Similar to Notch2, Id4 overexpression promotes DG NSC quiescence and Id4 knockdown rescues proliferation, even when Notch2 signaling is activated. We show that Notch2 regulates age-dependent DG NSC dormancy and Notch2 inhibition rejuvenates neurogenesis in the DG of aged mice. Our data indicate that a Notch2-Id4 axis promotes adult DG NSC quiescence and dormancy.

Suggested Citation

Zhang, Runrui and Boareto, Marcelo and Engler, Anna and Louvi, Angeliki and Giachino, Claudio and Iber, Dagmar and Taylor, Verdon, Notch2 Signaling Regulates Id4 and Cell Cycle Genes to Maintain Neural Stem Cell Quiescence in the Adult Hippocampus (2018). Available at SSRN: https://ssrn.com/abstract=3219279 or http://dx.doi.org/10.2139/ssrn.3219279
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Runrui Zhang

University of Basel - Embryology and Stem Cell Biology Lab

Petersplatz 1
Basel, CH-4003
Switzerland

Marcelo Boareto

Swiss Institute of Bioinformatics (SIB)

Mattenstrasse 26
CH-4058 Basel
Switzerland

Anna Engler

University of Basel - Embryology and Stem Cell Biology Lab

Petersplatz 1
Basel, CH-4003
Switzerland

Angeliki Louvi

Yale University - Department of Neuroscience

200 S Frontage Rd
New Haven, CT 06510
United States

Claudio Giachino

University Hospital Center Schleswig Holstein - Department of Neurosurgery

Kiel
Germany

Dagmar Iber

Swiss Institute of Bioinformatics (SIB)

Mattenstrasse 26
CH-4058 Basel
Switzerland

Verdon Taylor (Contact Author)

University of Basel - Department of Biomedicine

4056 Basel
Switzerland