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Reprogramming alters the gene expression in somatic cells, transforming them into induced pluripotent stem (iPS) cells over several generations. Scientists can reprogram cells by introducing genes for four transcription factors—Oct4, Sox2, Klf4, and c-Myc (OSKM) by viral or non-viral methods. These factors are also known as Yamanaka factors after Shinya Yamanaka, who first generated iPS cells using mouse skin cells. Yamanaka was awarded the Nobel Prize in Physiology or Medicine in 2012...
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Nuclear reprogramming is a process of transforming one cell type into an unrelated cell type by epigenetic changes that alter the cell’s original gene expression pattern. Such epigenetic changes force cells to express a different set of genes, which play a significant role in inducing transformation into other cell types. Nuclear reprogramming offers applications in reproductive cloning for livestock propagation and regenerative medicine — developing patient-specific cells for...
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The skin is divided into epidermis, dermis, and hypodermis, the skin's outermost, middle, and inner layers. The human epidermal layer regularly undergoes renewal, where old, dead cells are replaced by new cells. Epidermal stem cells or EpiSCs divide and differentiate to restore the lost cells. For the renewal process, some EpiSCs continuously self-renew. In contrast, few others differentiate into transit-amplifying cells, which later form prickle or spinous cells, followed by granular...
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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.

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    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.