マギ　シゲユキ   Magi Shigeyuki   間木　重行    所属   東邦大学  医学部 医学科    職種   助教
言語種別	英語
発表タイトル	A combination approach of pseudotime analysis and mathematical modeling for understanding drug-resistant mechanisms
会議名	The 81st Annual Meeting of the Japanese Cancer Association
学会区分	国内学会
発表形式	口頭
講演区分	一般
発表者・共同発表者	◎Magi S†, Naito AT†, Okada M
発表年月日	2022/10/01
開催地 （都市, 国名）	Yokohama, Japan
概要	The process of drug resistance acquisition remains largely unknown although the molecular mechanism of cancer drug resistance is well investigated. We elucidate the molecular mechanisms underlying the process of drug resistance acquisition by sequential analysis of gene expression patterns in tamoxifen-treated breast cancer cells. Single-cell RNA-sequencing indicates that tamoxifen-resistant cells were subgrouped into two, one showing altered gene expression related to metabolic regulation and another showing high expression levels of adhesion-related molecules and histone-modifying enzymes. Pseudotime analysis showed a cell transition trajectory to the two resistant subgroups that stem from a shared pre-resistant state. An ordinary differential equation model based on the trajectory fitted well with the experimental results of cell growth. Based on the established model, it was predicted and experimentally validated that inhibition of transition to both resistant subtypes would prevent the appearance of tamoxifen resistance. The main results are already published in the journal [1]. [1] Magi S., et al., Sci Rep 11, 18511 (2021)