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Updated: Aug 14, 2025
09:51
Assessing Cell Cycle Progression of Neural Stem and Progenitor Cells in the Mouse Developing Brain after Genotoxic Stress
Published on: May 7, 2014
15.4K
Interferon regulates neural stem cell function at all ages by orchestrating mTOR and cell cycle.
Damian Carvajal Ibañez1,2, Maxim Skabkin1, Jooa Hooli1,2,3
1Division of Molecular Neurobiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
EMBO Molecular Medicine
|January 13, 2023
Summary
Interferon signaling in stem cells protects against viruses but can impair brain stem cell activation with age. This pathway regulates Sox2, impacting quiescence and progenitor production, offering therapeutic potential for the aging brain.
Area of Science:
- Neuroscience
- Immunology
- Stem Cell Biology
Background:
- Stem cells possess intrinsic interferon signaling, conferring protection against viral infections across all ages.
- In the aging brain, interferon signaling has been observed to diminish stem cell activation capacity.
Purpose of the Study:
- To investigate the link between interferon's protective and inhibitory functions in stem cells.
- To elucidate the molecular mechanisms by which interferons regulate neural stem cell activation and progenitor production.
- To determine the temporal role of interferons in stem cell function.
Main Methods:
- Single-cell transcriptomics
- RiboSeq analysis
- Mathematical modeling of interferon pathways
Main Results:
- Interferon signaling is crucial for proper stem cell function throughout life in mice.
- Interferon orchestrates cell cycle and mTOR activity to repress Sox2 post-transcriptionally, inducing quiescence.
- The interferon response diminishes during subsequent maturation stages, with simulations suggesting age-dependent benefits and harms.
Conclusions:
- This study reveals molecular mechanisms of interferon action in stem cells.
- Interferons are regulators of stem cell homeostasis.
- Interferon pathways represent a potential therapeutic target for repairing the aging brain.
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