title: Rapid Reprogramming of Primary Human Astrocytes into Potent Tumor-Initiating Cells with Defined Genetic Factors.
abstract: 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 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.
authors.affiliation: Department of Dermatology, Duke University Medical Center, Durham, North Carolina.
authors.forename: Fang
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Dermatology, Duke University Medical Center, Durham, North Carolina.
authors.forename: Xinjian
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Duke University Medical Center, Durham, North Carolina. Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, North Carolina.
authors.forename: John H
authors.initials: JH
authors.lastname: Sampson
authors.affiliation: Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, North Carolina. Department of Pathology, Duke University Medical Center, Durham, North Carolina.
authors.forename: Darell D
authors.initials: DD
authors.lastname: Bigner
authors.affiliation: Department of Dermatology, Duke University Medical Center, Durham, North Carolina. Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina. chuan.li@duke.edu.
authors.forename: Chuan-Yuan
authors.initials: CY
authors.lastname: Li
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000473:pathology*; D018929:Cell Culture Techniques; D065150:Cellular Reprogramming / Q000235:genetics; D000067470:Cellular Reprogramming Techniques / Q000379:methods*; D005434:Flow Cytometry; D064593:Heterografts; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis