Glioma stem cells and their non-stem differentiated glioma cells exhibit differences in mitochondrial structure and function

Abstract

Although mitochondria play an important role in cell survival, their biological significance in differentiated and undifferentiated cells is not well known. In the present study, we compared the differences in the structure and function of mitochondria between undifferentiated cancer stem cells and differentiated cancer cells. Glioma stem cells (GSCs), when grown under serum culture conditions, demonstrated a decrease in stem cell marker expression and tumor sphere forming ability, while showing an increase in differentiated cell markers. Transmission electron microscopy analysis revealed that the number of mitochondria with distinct cristae and electron-dense matrices increased significantly in the non-stem differentiated glioma cells when compared to their undifferentiated GSCs. Bioinformatic analysis revealed that the glucose metabolic process gene signature was enriched in gene pools that had an increased number of stem cells. Additionally, qRT-PCR analysis revealed that the expression of various glucose metabolism genes was higher in GSCs than in non-stem differentiated glioma cells. Altogether, our results suggest that GSCs have immature mitochondria when compared to differentiated glioma cells. Notably, GSCs prefer a relatively higher glucose metabolism, which implies that they utilize different mitochondrial biosynthesis and metabolic pathways when compared to differentiated glioma cells.