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Publication : A transcriptional mechanism integrating inputs from extracellular signals to activate hippocampal stem cells.

First Author  Andersen J Year  2014
Journal  Neuron Volume  83
Issue  5 Pages  1085-97
PubMed ID  25189209 Mgi Jnum  J:217912
Mgi Id  MGI:5616046 Doi  10.1016/j.neuron.2014.08.004
Citation  Andersen J, et al. (2014) A transcriptional mechanism integrating inputs from extracellular signals to activate hippocampal stem cells. Neuron 83(5):1085-97
abstractText  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.
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