The properties of mitochondria in glioma stem cells

Abstract

Abstract Background Mitochondria have a key role in cell survival, signaling, metabolism, and homeostasis. However, whether their biological properties affected by differentiation status of cells are not well known. This study aimed to compare structural and functional differences of mitochondria between differentiated cancer cells and undifferentiated cancer stem cells. Methods Glioma stem cells (GSCs) were cultured in stem cell culture conditions to maintain their stem cell properties or serum culture conditions to induce their differentiation. Characteristics of GSCs are analyzed through sphere-forming ability and expression of stem cell/differentiation markers. Mitochondrial biogenesis and structure was examined by transmission electron microscopy analysis. Bioinformatics analysis, qRT-PCR, glucose uptake assay and lactate production assays were applied to reveal metabolic difference. Results GSCs grown in serum culture conditions showed lower stem cell markers expression and higher differentiation markers compared to GSCs grown in stem cell culture conditions. In the serum culture conditions, biogenesis of mitochondria was significantly increased. RNA sequencing analysis using GSCs grown in stem cell culture or serum culture conditions revealed that differentiated GSCs are enriched with mitochondria-related gene signature. Also, glucose metabolism was increased in GSCs grown in stem cell culture conditions compared to serum culture conditions. Conclusions Under different culture conditions, GSCs show different mitochondrial biogenesis and cellular metabolism. Understanding mitochondria properties in cancer may lead us to discover a novel therapeutic target. Editorial acknowledgement Cancer Growth Regulation Laboratory for technical support and helpful advice. Legal entity responsible for the study The authors. Funding National Research Foundation of Korea (NRF) [grant numbers: 2015R1A5A1009024 and 2017R1E1A1A01074205], the School of Life Sciences and Biotechnology for BK21 Plus, Korea University and Institute of Animal Molecular Biotechnology, Korea University. Disclosure All authors have declared no conflicts of interest.