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. Her; 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-beta 1). 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.

Automated summary

Members of the KDM5/JARID1 family have been found to be crucial in determining the fate of stem cells, with KDM5 inhibitor C70 (KDM5-C70) showing that the demethylase activity of KDM5 is essential in repressing astrocytic differentiation of neural stem cells (NSCs). Treatment with KDM5-C70 activated the Gfap gene and JAK-STAT3 signaling pathway, leading to astrocytogenesis in NSCs. This study provides evidence that KDM5 is a promising target for modulating NSC fate and highlights the importance of epigenetic regulation in determining NSC fate.