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Updated: Jun 15, 2025
09:17
Ex Utero Electroporation and Organotypic Slice Culture of Mouse Hippocampal Tissue
Published on: March 4, 2015
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Sequential transcriptional programs underpin activation of hippocampal stem cells
Piero Rigo1, Sara Ahmed-de-Prado1, Rebecca L Johnston2
1Neural Stem Cell Biology Laboratory, The Francis Crick Institute, London NW1 1AT, UK.
Science Advances
|June 11, 2025
Summary
Adult neural stem cells (NSCs) activate in stages. Ascl1 drives cells from deep to shallow quiescence, and Mycn promotes further progression toward proliferation, revealing a transcription factor code for NSC states.
Area of Science:
- Neuroscience
- Stem Cell Biology
- Molecular Biology
Background:
- Adult neural stem cells (NSCs) exhibit varying degrees of quiescence.
- Transitions between quiescent states are crucial for brain repair and aging.
- Transcription factors regulating these NSC transitions remain largely unknown.
Purpose of the Study:
- To identify transcription factors controlling stepwise transitions in adult hippocampal neural stem cell quiescence.
- To elucidate the role of Ascl1 in NSC activation from deep quiescence.
Main Methods:
- Single-cell transcriptomic analysis in mice.
- Loss-of-function and overexpression studies of the transcription factor Ascl1.
Main Results:
- Ascl1 promotes hippocampal NSC activation from deep quiescence.
- Ascl1 induces Mycn expression during the transition from deep to shallow quiescence.
- Mycn drives progression from shallow quiescence to a proliferating state.
Conclusions:
- Ascl1 and Mycn act sequentially to control NSC activation.
- A combinatorial code of transcription factors defines NSC quiescence states.
- This provides a framework for understanding NSC regulation in response to injury and aging.
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