Homo sapiens IPSCs Transcriptome

Down Syndrome (DS) is the most common autosomal aneuploidy caused by trisomy of chromosome 21. Previous studies demonstrated that DS affected mitochondrial functions, which may be related to abnormal development of the nervous system in DS. Runt-related transcription factor 1 (RunX1), an encoding gene located on chromosomal 21, is an important transcriptional regulator. It was reported that abnormal expression of RunX1 might affect cell apoptosis via the mitochondrial pathway. This study investigated whether RunX1 may play a critical role in the mitochondrial dysfunction of DS and how RunX1 affected mitochondrial functions. The expression level of RunX1 in DS-iPSCs was significantly higher than that in normal controls. Impaired mitochondrial functions were readily observed in DS-iPSCs. Significant changes, including damage of mitochondrial membrane potential, increased reactive oxygen species, and reduced ATP synthesis, were apparent. Interestingly, overexpression of RunX1 in normal iPSCs also resulted in mitochondrial dysfunction, while inhibition of RunX1 expression can improve the mitochondrial function in DS-iPSCs. Global gene expression study showed that overexpression of RunX1 might promote apoptosis in DS-iPSCs by affecting the PI3K/Akt pathway. The abnormal expression of RunX1 may play a critical factor in mitochondrial dysfunction in DS-iPSCs.