Progenitor cell-of-origin defines spatial and molecular presentation of glioblastoma. (A) Using inducible Cre recombinases driven by progenitor-specific promoter elements, such as nestin (NSC-selective) or NG2 (OPC-specific), progenitor cell-type–specific expression of wild-type IDHs, in the setting of identical driver mutations, may give rise to different high-grade glioma subtypes. (B, C) These tumors can be distinguished on histopathologic and molecular levels, including spatial presentation and the tumors' association with different transcriptomically defined subtypes. These studies support the idea that glioblastoma tumors have a “cell-of-origin memory” that defines tumor pheno- and genotypes (Alcantara Llaguno and Parada, 2016). Modified from figures 1 and 2 in reference Alcantara Llaguno et al. (2016). NG2, neuron-glial antigen 2; NSC, neural stem cell; OPC, oligodendrocyte precursor cell. Color images are available online.