Figure 4. MADM-generated glioma cells exhibit many OPC features.
(A) Representative image of a mutant-MADM brain carrying a GFP+ glioma.
(B–D) Adjacent H&E staining of tumor regions shows typical glioma features, including necrotic areas (“N “ in B), multinucleated giant cells (C), and peri-vascular satellitosis (D). Scale bars: (A), 2mm; (C and D), 200μm. Magnification in (B), 400×.
(E) Representative low magnification images show elevated expression of a panel of well-established glioma markers in tumor regions. All staining was done with adjacent sections from the same tumor. Tumor boundary is demarcated by dashed lines. T, tumor mass. Scale bars: 100μm except for CD9 staining, where it is 50μm.
(F) Quantitative RT-PCRs confirm the over-expression of OPC markers in MADM-generated glioma. (G–L) Confocal images at high magnification show that proliferating (Ki67+) green tumor cells express markers for OPCs (G–I, pointed by arrows) but not for other cell types (J–L). The signals of cell-type marker staining in the right column of (J–L) were converted to red for better examination of their co-localization with GFP. Some Ki67-negative green cells were CC1+ (circled in L). Scale bars: 20μm. (M) Transcriptome comparison between tumor samples and four neuroglial cell types (top four rows), and the four subtypes of human GBMs defined by TCGA (bottom four rows) with the single sample Gene Set Enrichment Analysis (ssGSEA) method. N and O represent tumor samples from mutant-MADM mice induced by NSC-Cre (Nestin-Cre or hGFAP-Cre) and by NG2-Cre, respectively; PDGFRα+ indicates primary tumor cells enriched by anti-PDGFRα immunopanning method. Color key: red to blue indicates significantly similar to dissimilar.
See also Figure S4.