Fig. 7.

Modulation of mtDNA copy number affects the fate of HSR-GBM1 cells. In the in vitro model of HSR-GBM1 cells, depletion of mtDNA (yellow arrow) for 7/14 days results in demethylation of the nuclear genome (green) and rescues differentiation to astrocytes that is otherwise blocked (green arrow). In the in vivo model of HSR-GBM1 cells, varying levels of depletion result in different frequencies of progression to tumorigenesis (orange arrow). 50% depletion accelerated tumorigenesis (thicker orange arrow), whereas further depletion slowed the initiation of tumorigenesis by modulating differentiation networks, nuclear gene expression and the mtDNA replication factors