Single cell RNAseq of murine gliomas induced by PDGFB overexpression

Glioblastoma progression remains elusive, especially in its first stages. Here, by simultaneous transfer of PDGFB and genetic barcode in mouse brain, we triggered gliomagenesis in univocally labelled cells in vivo, hence enabling direct tracing of glioblastoma evolution from the earliest possible stage. We observed an unexpectedly high incidence of clonal extinction events and progressive clonal size divergence, even after the acquisition of a malignant phenotype. Computational modelling suggests these dynamics as the consequence of a clonal-based cell-cell competition. Bulk and single-cell transcriptome analyses, coupled to lineage tracing, revealed that the strongest correlation with clonal size unbalancing is shown by Myc transcriptional targets. Additionally, higher levels of Myc signalling discriminate "winner" from "loser" clones in early gliomagenesis. These results agree with recent understanding of the Myc-mediated induction of supercompetitive phenotype in mammalian embryo. Our findings shed light on aspects of glioblastoma evolution inaccessible by conventional retrospective approaches and highlight the potential of the combined use of clonal tracing and transcriptomic analyses in this field. Gliomas induced by in-utero somatic gene transfer of PDGFB in embryonic telencephalic ventricles were collected at about 40 days from the birth. Tumor masses were dissociated, tumor cells were enriched by FACSorting exploiting the GFP expression. The resulting samples were pooled two by two prior to 10X partitioning.