Histone Lysine Demethylase KDM5 Inhibitor CPI-455 Induces Astrocytogenesis in Neural Stem Cells.
Thin Thin SanJunhyung KimHyun-Jung KimPublished in: ACS chemical neuroscience (2024)
Lysine-specific histone demethylase 5A (KDM5A) is known to facilitate proliferation in cancer cells and maintain stemness to repress the astrocytic differentiation of neural stem cells (NSCs). In the study presented here, we investigated the effect of a KDM5 inhibitor, CPI-455, on NSC fate control. CPI-455 induced astrocytogenesis in NSCs during differentiation. Kdm5a , but not Kdm5c , knockdown induced glial fibrillary acidic protein ( Gfap ) transcription. CPI-455 induced signal transducer and activator of transcription 3, increased bone morphogenetic protein 2 expression, and enhanced mothers against decapentaplegic homolog 1/5/9 phosphorylation. The treatment of CPI-455 enhanced the methylation of histone H3 lysine 4 in the Gfap promoter when compared to that of the dimethyl sulfoxide control. In addition, CPI-455 treatment significantly reduced the recruitment of KDM5A to the Gfap promoter. Our data suggest that the KDM5 inhibitor CPI-455 effectively controls NSC cell fate via KDM5A inhibition and induces astrocytogenesis.
Keyphrases
- neural stem cells
- dna methylation
- high glucose
- transcription factor
- diabetic rats
- gene expression
- cell fate
- stem cells
- drug induced
- poor prognosis
- signaling pathway
- spinal cord injury
- epithelial mesenchymal transition
- machine learning
- endothelial cells
- spinal cord
- neuropathic pain
- small molecule
- high resolution
- inflammatory response
- stress induced
- replacement therapy