Image depicting GSGs originating from mutated NSCs (1). Depending on specific environmental cues (2), the “GSC of origin” will undergo either asymmetric or symmetric cell division to give rise to, respectively, self-renewed GSCs and differentiated non-GSCs (3). This will ultimately lead to a genetically and phenotypically heterogeneous GBM. The plastic phenotype is seen by the interconversion between GSCs and non-GSCs (4). Non-mutated neural progenitor cells will originate a wide range of cells in the brain, such as astrocytes, glia cell, and neurons (5).