KDM4C promotes mouse hippocampal neural stem cell proliferation through modulating ApoE expression

Area of Science:

• Neuroscience
• Stem Cell Biology
• Molecular Biology

Background:

• KDM4C regulates stem cell functions but its role in neural stem cells (NSCs) is unclear.
• Understanding KDM4C in NSCs is crucial for neurodevelopmental research.

Purpose of the Study:

• Investigate the function and regulatory mechanism of KDM4C in mouse hippocampal NSCs.
• Elucidate the molecular pathways influenced by KDM4C in neurogenesis.

Main Methods:

• Lentivirus-mediated KDM4C overexpression in primary hippocampal NSCs (in vivo and in vitro).
• Cell proliferation assays (BrdU, Ki-67, S-phase analysis).
• RNA sequencing (RNA-seq), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, Gene Set Enrichment Analysis (GSEA), and protein-protein interaction analysis.

Main Results:

• KDM4C overexpression significantly increased NSC proliferation and cell cycle progression.
• RNA-seq identified KDM4C-regulated genes involved in development, cell cycle, and neurogenesis.
• ApoE was identified as a key interacting protein, mediating KDM4C's proliferative effects.

Conclusions:

• KDM4C promotes mouse hippocampal NSC proliferation through ApoE upregulation.
• This study reveals a novel KDM4C-ApoE pathway regulating neurogenesis.
• Findings have implications for understanding neurodevelopment and treating neurological disorders.