P53 controls genomic stability and temporal differentiation of human neural stem cells and affects neural organization in human brain organoids.

ABSTRACT: In this study, we take advantage of human induced pluripotent stem (iPS) cell-derived neural stem cells and brain organoids 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. Furthermore, a reduced proliferation rate, downregulation of genes involved in oxidative phosphorylation (OXPHOS), and an upregulation of glycolytic capacity was apparent upon loss of p53. In addition, p53KD neural stem cells display an increased pace of differentiating into neurons and exhibit a phenotype corresponding to more mature neurons compared to control neurons. Using brain organoids, we modeled more specifically cortical neurogen

SUBMITTER: Marin Navarro A 

PROVIDER: S-EPMC6978389 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature