Supplementary Fig. S1. Supplementary Fig. 1 related to Fig.1 Transformation scheme and expression of external genes in transformed cells. Supplementary Fig. S2. Supplementary Fig. 2 related to Fig. 1. GEO analysis of gene expression patterns of transformed human astrocytes. Supplementary Fig. S3. Supplementary Fig. 3 related to Fig. 2. Chromosome aberration analysis and hTERT gene expression in transformed astrocytes. Supplementary Fig. S4. Supplementary Fig. S4 related to Fig. 4. In vivo growth of transformed astrocytes in nude mice. Supplementary Table S1. Source of antibodies used in the current study. Supplementary Methods. Additional details of experimental methods used in this study
ARTICLE ABSTRACTCancer 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 transduced 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. Finally, they also displayed resistance to the widely used brain cancer drug temozolomide. These iCSCs could provide important tools for studies of glioma biology and therapeutics development. Cancer Res; 76(17); 5143–50. ©2016 AACR.