The KDM5 Inhibitor KDM5-C70 Induces Astrocyte Differentiation in Rat Neural Stem Cells

Members of the lysine-specific histone demethylase 5 (KDM5/JARID1) family are known to play important roles in stem cell fate determination. Here, using the KDM5 inhibitor C70 (KDM5-C70), we demonstrated that the histone demethylase activity of the KDM5 enzyme is essential for the repression of astr...

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Published inACS chemical neuroscience Vol. 12; no. 3; pp. 441 - 446
Main Authors Lee, Ha-Rim, Ann, Jihyae, Kim, Young Min, Lee, Jeewoo, Kim, Hyun-Jung
Format Journal Article
LanguageEnglish
Published United States American Chemical Society 03.02.2021
Subjects
astrocyte differentiation
histone modification
KDM5-C70
histone demethylase
rat neural stem cells
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Summary:Members of the lysine-specific histone demethylase 5 (KDM5/JARID1) family are known to play important roles in stem cell fate determination. Here, using the KDM5 inhibitor C70 (KDM5-C70), we demonstrated that the histone demethylase activity of the KDM5 enzyme is essential for the repression of astrocytic differentiation of neural stem cells (NSCs). KDM5-C70 treatment activated the glial fibrillary acidic protein (Gfap) gene by increasing the trimethylation of histone H3 lysine 4 in the promoter regions and subsequently induced astrocytogenesis in NSCs. In addition, treatment of NSCs with KDM5-C70 activated Janus kinase-signal transducer and activator of transcription (JAK-STAT3) signaling and increased the mRNA expression of transforming growth factor-beta 1 (Tgf-β1). Our data provide evidence that KDM5 is a promising target for NSC fate modulation and suggest that epigenetic regulation is important for NSC fate determination.
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ISSN:1948-7193
1948-7193
DOI:10.1021/acschemneuro.0c00613