Description
In this study, we take advantage of human induced pluripotent stem (iPS) cell-derived neural stem cells to study the role of p53 during human brain development. We knocked down (KD) p53 in human neuroepithelial stem (NES) cells derived from iPS cells. Upon p53KD, NES cells rapidly show centrosome amplification and genomic instability. Gene expression analysis show downregulation of genes involved in oxidative phosphorylation (OXPHOS) upon loss of p53. In addition, p53KD neural stem cells upregulate genes involved in neuronal differentiation and display an increased pace of differentiating into neurons and exhibit a phenotype corresponding to more mature neurons compared to control neurons. Taken together, this demonstrates an important role for p53 in controlling genomic stability of neural stem cells and regulation of neuronal differentiation.