GSE123428
ROS control in human iPS cells reveals early events in spontaneous carcinogenesis
We developed a system to control the intracellular level of reactive oxygen species (ROS) in human iPS cells. By introducing a specific substitution (I69E) into the SDHC protein, a component of the mitochondrial respiratory chain complex, the intracellular ROS level considerably increased. This caused an abnormal development of iPS cells, and these abnormalities were reverted by the overproduction of mitochondria-targeted catalase. When ROS-overproducing iPS cells (ChiPSC12-M cells) were used for subcutaneous inoculation on the backs of nude mice, the mice exhibited tumor formation. The expression of tumor-related FOXC1 transcription factor increased as early as 4 h after the the development of ROS-overproducing iPS cells was initiated. An RNA-seq analysis revealed that 27 transcript clusters among the more than 20,000 transcrips that were examined were highly expressed at 4 h after the initiation of tumor development in ChiPSC12-M cells. Some of these overexpressed transcripts might make networks to activate protooncogenes for spontaneous carcinogenesis. Overall design: ChiPSC12-M was cultured with Day 0 endoderm differentiation medium and the medium was replaced with Day 1 differentiation medium with or without Tet-Express solution and the cells were cultured for 4 h. Total RNA from each cell was isolated using Isogen (Nippon Gene Co., Ltd, Toyama, Japan) and was subjected to RNA-Sequencing (Cell Innovator, Kyushu Univ., Fukuoka, Japan).