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Id4 Eliminates the Pro-Activation Factor Ascl1 to Maintain Quiescence of Adult Hippocampal Stem Cells

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

See all articles by Isabelle Blomfield

Isabelle Blomfield

Francis Crick Institute

Brenda Rocamonde

Sorbonne University - Brain and Spinal Cord Institute

Maria del Mar Masdeu

Francis Crick Institute

Eskeatnaf Mulugeta

Erasmus University Rotterdam (EUR) - Department of Cell Biology

Stefania Vaga

Francis Crick Institute

Debbie L. C. van den Berg

Erasmus University Rotterdam (EUR) - Department of Cell Biology

Emmanuelle Huillard

Sorbonne University - Brain and Spinal Cord Institute

Noelia Urbán

Francis Crick Institute

Francois Guillemot

Francis Crick Institute

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Abstract

Quiescence is essential for the long-term maintenance of adult stem cells and tissue homeostasis. However, how stem cells maintain quiescence is still poorly understood. Here we show that stem cells in the dentate gyrus of the adult hippocampus actively transcribe the pro-activation factor Ascl1 regardless of their activation state. We found that the inhibitor of DNA binding protein Id4 suppresses Ascl1 activity in neural stem cell cultures. Id4 sequesters Ascl1 heterodimerisation partner E47, promoting Ascl1 protein degradation and neural stem cell quiescence. Accordingly, elimination of Id4 from stem cells in the adult hippocampus results in abnormal accumulation of Ascl1 protein and premature stem cell activation. We also found that multiple signalling pathways converge on the regulation of Id4 to reduce the activity of hippocampal stem cells. Id4 therefore maintains quiescence of adult neural stem cells, in sharp contrast with its role of promoting the proliferation of embryonic neural progenitors.

Suggested Citation

Blomfield, Isabelle and Rocamonde, Brenda and Masdeu, Maria del Mar and Mulugeta, Eskeatnaf and Vaga, Stefania and van den Berg, Debbie L. C. and Huillard, Emmanuelle and Urbán, Noelia and Guillemot, Francois, Id4 Eliminates the Pro-Activation Factor Ascl1 to Maintain Quiescence of Adult Hippocampal Stem Cells (2018). Available at SSRN: https://ssrn.com/abstract=3219271 or http://dx.doi.org/10.2139/ssrn.3219271
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Isabelle Blomfield

Francis Crick Institute

1 Midland Road
London, NW1 1AT
United Kingdom

Brenda Rocamonde

Sorbonne University - Brain and Spinal Cord Institute

Paris, F‐75013
France

Maria del Mar Masdeu

Francis Crick Institute

1 Midland Road
London, NW1 1AT
United Kingdom

Eskeatnaf Mulugeta

Erasmus University Rotterdam (EUR) - Department of Cell Biology

Doctor Molewaterplein 40
Rotterdam, South Holland 3015 GD
Netherlands

Stefania Vaga

Francis Crick Institute

1 Midland Road
London, NW1 1AT
United Kingdom

Debbie L. C. Van den Berg

Erasmus University Rotterdam (EUR) - Department of Cell Biology

Doctor Molewaterplein 40
Rotterdam, South Holland 3015 GD
Netherlands

Emmanuelle Huillard

Sorbonne University - Brain and Spinal Cord Institute

Paris, F‐75013
France

Noelia Urbán

Francis Crick Institute ( email )

1 Midland Road
London, NW1 1AT
United Kingdom

Francois Guillemot (Contact Author)

Francis Crick Institute ( email )

1 Midland Road
London, NW1 1AT
United Kingdom

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