Human pluripotent stem cell-derived brain tumor model uncovered embryonic stem cell signature as a key driver in atypical teratoid/rhabdoid tumor (RNA-Seq)
收藏干细胞与再生医学数据中心2022-02-20 更新2024-03-06 收录
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Atypical teratoid/rhabdoid tumor (AT/RT), which harbors INI1 mutation and exhibits a characteristic histology of rhabdoid cells, has a poor prognosis because of the lack of effective treatments. Here we established human INI1-deficient pluripotent stem cells (hPSCs), which developed AT/RT formation in vivo. We revealed that the activation of ESC-like signature leads to rhabdoid phenotype in tumor by OSKM or c-MYC induction. Finally, we performed CRISPR/Cas9 knockout screening to inhibit activation of ESC-like signature in AT/RT. Our effort identified candidate genes including RAD21 that encodes a key component within the cohesin complex. Notably, chemical inhibition of HDAC8 that indirectly targets the function of cohesin with simultaneous inhibition of EZH2 efficiently suppressed the activation of ESC-like signature and inhibited the growth of AT/RT cells both in vitro and in vivo.
提供机构：
University of Tokyo
创建时间：
2022-02-20
