Generating cancer stem cells from primary human astrocytes

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.

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