Lysine-specific histone demethylase 1A (KDM1A/LSD1) inhibition attenuates DNA double strand break repair and augments efficacy of temozolomide in glioblastoma

To understand the mechanistic insights on how KDM1A inhibition sensitizes glioblastoma (GBM) to temozolomide, we performed genome wide localization studies of KDM1A in patient derived glioma stem cells (GSCs) using CUT&Tag-seq. GSC082209 (GSC08) cells were treated with vehicle or NCD38 (5 μM) for 24 h and 250,000 cells per condition were used. Data analysis on CUT&Tag sequencing reads was performed by the nf-core/cutandrun bioinformatic analysis pipeline. We detected 75,491 KDM1A peaks in the genome of GSCs (p<0.0001). Pathway analysis of KDM1A binding genes using Gene Ontology showed KDM1A binding genes were enriched in DNA repair, cell cycle, and UPR signaling pathways . CUT&Tag sequencing for KDM1A in patient derived glioma stem cells. Gangadhara Sareddy