Dynamic changes in mitochondrial biogenesis and antioxidant enzymes during the spontaneous differentiation of human embryonic stem cells.
Embryonic cells before implantation are exposed to a hypoxic condition and dependent on anaerobic metabolism. Human embryonic stem cells (HESCs) derived from pre-implantation blastocyst also grow well in hypoxic conditions. Expecting that the differentiating HESCs might mimic anaerobic-to-aerobic metabolic transition of the early human life, we examined the mitochondria-related changes in these cells. We observed that mitochondrial mass and mitochondrial DNA content were increased with differentiation, which was accompanied by the increase of the amount of ATP (4-fold) and its by-product reactive oxygen species (2.5-fold). The expression of various antioxidant enzymes including mitochondrial and cytoplasmic superoxide dismutases, catalase, and peroxiredoxins showed a dramatic change during the early differentiation. In conclusion, HESC differentiation was followed by dynamic changes in mitochondrial mass, ATP and ROS production, and antioxidant enzyme expressions. Therefore, the HESCs would serve as a good model to examine the mitochondrial biology during the early human differentiation.
Cho
Young Min
YM
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea. ymchomd@snu.ac.kr
Kwon
Sujin
S
Pak
Youngmi Kim
YK
Seol
Hye Won
HW
Choi
Young Min
YM
Park
Do Joon
DJ
Park
Kyong Soo
KS
Lee
Hong Kyu
HK
D000255:Adenosine Triphosphate / Q000378:metabolism; D000975:Antioxidants / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D004272:DNA, Mitochondrial / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology*; D004798:Enzymes / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D024101:Mitochondrial Proteins / Q000378:metabolism; D010085:Oxidative Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism*
D000975:Antioxidants; D004272:DNA, Mitochondrial; D004798:Enzymes; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate