The anatomical location and cell type from which tumours originate has biological, diagnostic and therapeutic implications, but understanding how a tumour forms in humans is challenging. Classical approaches for studying cancer-initiating cells often involve introducing cell type-specific mutations in animal models and then observing which mutated cell types lead to tumour formation. However, some tumours, such as the deadly glioblastoma (GBM), are characterized by a high cellular, molecular and phenotypic heterogeneity that complicates efforts to identify the anatomical origin and cell type in which the tumour originated. In addition, differences between human patients and the non-human experimental models may exist, as cellular heterogeneity and behaviour can be different between species, especially in the brain.

“differences between human patients and the non-human experimental models may exist”