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

Author:

Zhu Kun1ORCID,Zhang Hanyue2ORCID,Luan Yan2ORCID,Hu Baoqi3ORCID,Shen Tu24ORCID,Ma Bo3ORCID,Zhang Zhichao2ORCID,Zheng Xiaoyan5ORCID

Affiliation:

1. Department of Neurology The First Affiliated Hospital of Xi'an Jiaotong University Xi'an Shaanxi China

2. Institute of Neurobiology Xi'an Jiaotong University Health Science Center Xi'an Shaanxi China

3. Department of Ophthalmology The First Affiliated Hospital of Xi'an Jiaotong University Xi'an Shaanxi China

4. The Medical Services Section The First Affiliated Hospital of Jinzhou Medical University Jinzhou Liaoning China

5. Department of Hematology The First Affiliated Hospital of Xi'an Jiaotong University Xi'an Shaanxi China

Abstract

AbstractKDM4C is implicated in the regulation of cell proliferation, differentiation, and maintenance in various stem cell types. However, its function in neural stem cells (NSCs) remains poorly understood. Therefore, this study aims to investigate the role and regulatory mechanism of KDM4C in NSCs. Primary hippocampal NSCs were isolated from neonatal mice, and both in vivo and in vitro lentivirus‐mediated overexpression of KDM4C were induced in these hippocampal NSCs. Staining results revealed a significant increase in BrdU‐ and Ki‐67‐positive cells, along with an elevated number of cells in S phases due to KDM4C overexpression. Subsequently, RNA‐seq was employed to analyze gene expression changes following KDM4C upregulation. GO enrichment analysis, KEGG analysis, and GSEA highlighted KDM4C‐regulated genes associated with development, cell cycle, and neurogenesis. Protein‐protein interaction analysis uncovered that ApoE protein interacts with several genes (top 10 upregulated and downregulated) regulated by KDM4C. Notably, knocking down ApoE mitigated the proliferative effect induced by KDM4C overexpression in NSCs. Our study demonstrates that KDM4C overexpression significantly upregulates ApoE expression, ultimately promoting proliferation in mouse hippocampal NSCs. These findings provide valuable insights into the molecular mechanisms governing neurodevelopment, with potential implications for therapeutic strategies in neurological disorders.

Funder

National Natural Science Foundation of China

Fundamental Research Funds for the Central Universities

Key Research and Development Projects of Shaanxi Province

Publisher

Wiley

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