This transcriptomic dissection of glioma heterogeneity was functionally validated with the observation that Zfp423 exerts the strongest antigliomagenic activity only in the context of the least tumour-primed astrocytes, in which it antagonizes, in an exquisitely SMAD signalling-dependent manner, a very significant portion of the gliomagenic programme that includes Sox2, a well-established glioma oncogene, and several other differentiation-promoting factors that are specifically downregulated in gliomas. The gene discussed is SOX2; the disease is central nervous system cancer.