title: Signals that regulate the oncogenic fate of neural stem cells and progenitors.
abstract: Brain tumors have frequently been associated with a neural stem cell (NSC) origin and contain stem-like tumor cells, so-called brain tumor stem cells (BTSCs) that share many features with normal NSCs. A stem cell state of BTSCs confers resistance to radiotherapy and treatment with alkylating agents. It is also a hallmark of aggressive brain tumors and is maintained by transcriptional networks that are also active in embryonic stem cells. Advances in reprogramming of somatic cells into induced pluripotent stem (iPS) cells have further identified genes that drive stemness. In this review, we will highlight the possible drivers of stemness in medulloblastoma and glioma, the most frequent types of primary malignant brain cancer in children and adults, respectively. Signals that drive expansion of developmentally defined neural precursor cells are also active in corresponding brain tumors. Transcriptomal subgroups of human medulloblastoma and glioma match features of NSCs but also more restricted progenitors. Lessons from genetically-engineered mouse (GEM) models show that temporally and regionally defined NSCs can give rise to distinct subgroups of medulloblastoma and glioma. We will further discuss how acquisition of stem cell features may drive brain tumorigenesis from a non-NSC origin. Genetic alterations, signaling pathways, and therapy-induced changes in the tumor microenvironment can drive reprogramming networks and induce stemness in brain tumors. Finally, we propose a model where dysregulation of microRNAs (miRNAs) that normally provide barriers against reprogramming plays an integral role in promoting stemness in brain tumors.
authors: Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
authors: Fredrik J
authors: FJ
authors: Swartling
authors: Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
authors: Sara
authors: S
authors: Bolin
authors: Department of Neurological Surgery, Brain Tumor Research Center, University of California, San Francisco, USA; Department of Pathology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, USA.
authors: Joanna J
authors: JJ
authors: Phillips
authors: Department of Neurological Surgery, Brain Tumor Research Center, University of California, San Francisco, USA; Department of Neurology, Sandler Neurosciences Center, University of California, San Francisco, USA. Electronic address: Anders.Persson@ucsf.edu.
authors: Anders I
authors: AI
authors: Persson
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D006801:Humans; D058953:Neural Stem Cells / Q000166:cytology*; D015398:Signal Transduction / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology*
keywords: Brain tumor; Glioma; Medulloblastoma; Neural stem cell; Progenitor; Reprogramming; miRNA
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