Repository with code to reproduce analyses and figures in "Glioblastoma cells co-opt epigenetic regulators of normal oligodendrocyte development for brain infiltration"
Glioblastoma (GBM) is a highly aggressive brain tumor known for its ability to infiltrate and colonize normal brain tissue. Despite the clinical relevance of this behavior, the molecular characteristics of infiltrating GBM cells in the peritumoral zone remain largely unexplored in patients. Here, we show that peritumoral progenitor-like GBM cells overexpress transcriptional programs associated with increased neuronal migration, synaptic activity, and NOTCH signaling. Moreover, they spatially colocalize with neurons and have increased propensity for neuronal crosstalk. These infiltrative cells hijack key transcription factors that typically direct normal oligodendrocyte progenitor cell (OPC) differentiation. We further demonstrate that the epigenetic encoding of these infiltrative cells mirrors that of uncommitted OPCs in the developing human brain, a neurodevelopmental state marked by increased synaptic and migratory capabilities. Our findings provide critical insights into the neurodevelopmental hijacking that drives GBM infiltration in patients, rationalizing further investigation into targeting differentiation potential as a therapeutic strategy.
Lead contact for data and materials availability: federico.gaiti@uhn.ca