利用双内源报告员系统来识别异常干细胞的功能调节剂和结直肠癌中的分化活性
Sandor Spisak1,2, David Chen1,3, Pornlada Likasitwatanakul1,4,5,6
1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
bioRxiv : the preprint server for biology
|January 31, 2024
概括
研究人员确定SMARCB1是结直肠癌 (CRC) 细胞分化的关键调节者. 这一发现来自于一种新型报告系统和CRISPR屏幕,突出显示SMARCB1是CRC的潜在治疗标.
科学领域:
- 癌症生物学 癌症生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 干细胞生物学 干细胞生物学
背景情况:
- 异常的干细胞样活动和受损的分化是结直肠癌 (CRC) 发展的标志.
- 识别这些细胞过程的调节者对于理解CRC病原体和开发新疗法至关重要.
研究的目的:
- 确定调节干细胞类活性和结直肠癌分化功能的介质.
- 为了利用一种新的内源报告系统和基因选器来发现目标.
主要方法:
- 在人类CRC细胞系中开发了一种内源双记者系统,用于监测干细胞活性 (SOX9) 和分化 (KRT20).
- 进行了聚合的CRISPR选,针对78个表观遗传调节器.
- 使用扰乱单细胞RNA测序 (Perturb-seq) 来验证匹配结果.
主要成果:
- 双报告员系统增强了用于蜂活动监控的信号噪声区分.
- 克里斯普尔查确定了影响CRC干和分化的关键表观遗传调节者.
- 作为BAF复合物的组成部分,SMARCB1被确定为分化的一个关键的负调节器,在体内对CRC生长至关重要.
结论:
- 开发的内源性报告员系统有效地发现了CRC中的新型治疗点.
- 在结直肠癌中,SMARCB1具有显著的依赖性,突出了其作为药物开发治疗点的潜力.
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