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Isolation and Cultivation of Neural Progenitors Followed by Chromatin-Immunoprecipitation of Histone 3 Lysine 79 Dimethylation Mark
Published on: January 26, 2018
Histone demethylase LSD1 regulates neural stem cell proliferation
GuoQiang Sun1, Kamil Alzayady, Richard Stewart
1Department of Neurosciences, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA.
Molecular and Cellular Biology
|February 4, 2010
Summary
Lysine-specific demethylase 1 (LSD1) is crucial for neural stem cell proliferation. LSD1, regulated by TLX, controls gene expression impacting cell growth, revealing a new mechanism for neural stem cell regulation.
Area of Science:
- Neuroscience
- Epigenetics
- Stem Cell Biology
Background:
- Lysine-specific demethylase 1 (LSD1) is a transcriptional coregulator involved in histone methylation.
- The function of LSD1 in neural stem cells (NSCs) remains largely unexplored.
Purpose of the Study:
- To investigate the role of LSD1 in regulating NSC proliferation.
- To elucidate the mechanism by which LSD1 influences NSC growth.
Main Methods:
- Inhibition of LSD1 activity and knockdown of LSD1 expression in NSCs.
- Viral transduction of LSD1 small interfering RNA (siRNA) in adult mouse brains.
- Administration of LSD1 inhibitors (pargyline, tranylcypromine) to mice.
- Analysis of neural progenitor proliferation in the hippocampal dentate gyrus.
- Gene expression analysis of TLX target genes.
Main Results:
- LSD1 inhibition or knockdown significantly reduced NSC proliferation.
- LSD1 is recruited by the nuclear receptor TLX to repress proliferation-related genes.
- In vivo administration of LSD1 inhibitors decreased neural progenitor proliferation in adult mouse brains.
- TLX knockout abolished the inhibitory effects of LSD1 inhibitors on neural progenitor proliferation.
Conclusions:
- LSD1 is a key regulator of neural stem cell proliferation.
- LSD1 functions in conjunction with TLX to control NSC growth by modulating gene expression.
- This study uncovers a novel mechanism for LSD1-mediated regulation of neural stem cell proliferation via TLX activity.
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