Rapid Reprogramming of Primary Human Astrocytes into Potent Tumor-Initiating Cells with Defined Genetic Factors.
Rapid Reprogramming of Primary Human Astrocytes into Potent Tumor-Initiating Cells with Defined Genetic Factors.
复制标题
DOI：
10.1158/0008-5472.can-16-0171
复制
发表时间：
2016-09-01
期刊：
影响因子：
11.2
通讯作者：
Li CY
中科院分区：
文献类型：
--
作者：
Li F;Liu X;Sampson JH;Bigner DD;Li CY
癌症干细胞样细胞（CSC）被认为是脑癌的驱动因素，但它们的细胞和分子起源仍然不确定。在这里，我们报告了通过表达确定的遗传因子从原代人星形胶质细胞成功产生诱导CSC（iCSC）。联合转导四种因子- myc、Oct-4、p53 DD和ras -诱导原代人星形胶质细胞有效转化为具有强大肿瘤起始能力的恶性细胞。值得注意的是，将100个转导的细胞移植到裸鼠中足以形成肿瘤。细胞具有无限的自我更新能力，端粒酶活性强。此外，它们表达典型的胶质瘤干细胞样细胞标志物，如CD 133、CD 15和CD 90。此外，这些细胞在培养中可以形成球体并分化为神经元样细胞、星形胶质细胞样细胞和少突胶质细胞样细胞。最后，他们还显示出对广泛使用的脑癌药物替莫唑胺的耐药性。这些iCSC可为胶质瘤生物学研究和治疗药物开发提供重要工具。
Cancer stem-like cells (CSC) are thought to drive brain cancer but their cellular and molecular origins remain uncertain. Here we report the successful generation of induced CSC (iCSC) from primary human astrocytes through the expression of defined genetic factors. Combined transduction of four factors - myc, Oct-4, p53DD, and ras - induced efficient transformation of primary human astrocytes into malignant cells with powerful tumor-initiating capabilities. Notably, transplantation of 100 tranduced cells into nude mice was sufficient for tumor formation. The cells showed unlimited self-renewal ability with robust telomerase activities. In addition, they expressed typical glioma stem-like cell markers such as CD133, CD15 and CD90. Moreover, these cells could form spheres in culture and differentiate into neuron-like, astrocyte-like and oligodendrocyte-like cells. Lastly, they also displayed resistance to the widely used brain cancer drug temozolomide. These iCSC could provide important tools for studies of glioma biology and therapeutics development.