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Updated: Jul 19, 2025

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在单细胞分辨率上进行YAP驱动的口腔上皮层干细胞恶性重编程
bioRxiv : the preprint server for biology
|August 7, 2023
概括
研究人员在口腔上皮细胞中捕获了癌症的早期发展,揭示了具有干状性质的瘤发起细胞 (TIC). 这些TIC驱动瘤生长和入侵,为早期癌症检测和预防提供了新的目标.
科学领域:
- 癌症生物学 癌症生物学
- 细胞重编程 细胞重编程
- 多种组合的多种组合.
背景情况:
- 瘤发育始于正常的原生细胞转化为癌症.
- 在体内观察早期瘤启动仍然具有挑战性.
研究的目的:
- 以单细胞分辨率揭示口腔上皮原生细胞转化为瘤发起细胞 (TIC) 的重编程过程.
- 确定早期口腔癌发展中的分子机制和保存途径.
主要方法:
- 空间时间控制的瘤基因激活和瘤抑制剂抑制 in vivo.
- 单细胞分辨率的多组学分析.
- 调查YAP介导的转录网络和细胞信号传输.
主要成果:
- 鉴定了具有明显的茎状状态的TIC,其特征是异常的增殖,缺氧,状分化和部分上皮细胞到介质细胞转变 (pEMT).
- 在TIC中YAP激活促进了瘤转录,mTOR信号传递和髓状细胞向侵袭前线招募.
- 在人类头癌中,TIC转录程序被保留,与患者的生存率差相关.
结论:
- 阐明了癌症启动和TIC重编程的单细胞分离过程.
- 突出了YAP信号在驱动TIC表型和瘤透中的作用.
- 在头癌中确定了保存的ICT程序,这表明了早期检测和预防的潜在目标.
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