主讲人：吴华君  北京大学研究员

时间：2021年3月22日14：00

地点：三号楼332会议厅

举办单位：数理学院

内容介绍：Members of the KDM5 histone H3 lysine 4 demethylase family are associated with  therapeutic resistance, including endocrine resistance in breast cancer, but the  underlying mechanism is poorly defined. Here we show that genetic deletion of  KDM5A/B or inhibition of KDM5 activity increases sensitivity to anti-estrogens  by modulating estrogen receptor (ER) signaling and by decreasing cellular  transcriptomic heterogeneity. Higher KDM5B expression levels are associated with  higher transcriptomic heterogeneity and poor prognosis in ER+ breast tumors.  Single-cell RNA sequencing, cellular barcoding, and mathematical modeling  demonstrate that endocrine resistance is due to selection for pre-existing  genetically distinct cells, while KDM5 inhibitor resistance is acquired. Our  findings highlight the importance of cellular phenotypic heterogeneity in  therapeutic resistance and identify KDM5A/B as key regulators of this process.