A Transcriptional Mechanism Integrating Inputs from Extracellular Signals to Activate Hippocampal Stem Cells
Neuron. 2014-09-01; 83(5): 1085-1097
DOI: 10.1016/j.neuron.2014.08.004
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1. Neuron. 2014 Sep 3;83(5):1085-97. doi: 10.1016/j.neuron.2014.08.004.
A transcriptional mechanism integrating inputs from extracellular signals to
activate hippocampal stem cells.
Andersen J(1), Urbán N(2), Achimastou A(1), Ito A(1), Simic M(3), Ullom K(3),
Martynoga B(1), Lebel M(1), Göritz C(4), Frisén J(4), Nakafuku M(3), Guillemot
F(5).
Author information:
(1)Division of Molecular Neurobiology, MRC National Institute for Medical
Research, Mill Hill, London NW7 1AA, UK.
(2)Division of Molecular Neurobiology, MRC National Institute for Medical
Research, Mill Hill, London NW7 1AA, UK. Electronic address:
.
(3)Division of Developmental Biology, Cincinnati Children’s Hospital Research
Foundation, Cincinnati, OH 45229-3039, USA.
(4)Department for Cell and Molecular Biology, Karolinska Institute, 17177
Stockholm, Sweden.
(5)Division of Molecular Neurobiology, MRC National Institute for Medical
Research, Mill Hill, London NW7 1AA, UK. Electronic address:
.
The activity of adult stem cells is regulated by signals emanating from the
surrounding tissue. Many niche signals have been identified, but it is unclear
how they influence the choice of stem cells to remain quiescent or divide. Here
we show that when stem cells of the adult hippocampus receive activating
signals, they first induce the expression of the transcription factor Ascl1 and
only subsequently exit quiescence. Moreover, lowering Ascl1 expression reduces
the proliferation rate of hippocampal stem cells, and inactivating Ascl1 blocks
quiescence exit completely, rendering them unresponsive to activating stimuli.
Ascl1 promotes the proliferation of hippocampal stem cells by directly
regulating the expression of cell-cycle regulatory genes. Ascl1 is similarly
required for stem cell activation in the adult subventricular zone. Our results
support a model whereby Ascl1 integrates inputs from both stimulatory and
inhibitory signals and converts them into a transcriptional program activating
adult neural stem cells.
Copyright © 2014 Elsevier Inc. All rights reserved.
DOI: 10.1016/j.neuron.2014.08.004
PMCID: PMC4157576
PMID: 25189209 [Indexed for MEDLINE]