Project 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. We used microarrays to identify gene expression changes in human NES cells upon p53 knockdown
Project description:We report the transcriptional profile of human spinal cord and neocortical neuroepithelial stem cells (SC-NES and NCX-NES cells) to identify potential engraftment markers in the lesioned spinal cord. We report that cells with a homologous neuroanatomical origin robustly integrate in the host tissue compared to cells with a different regional identity. Specifically, we describe that SC-NES cells display elective integration properties in the lesioned spinal cord compared to NCX-NES cells and that these properties are due to a combination of intrinsic and extrinsic factors. Upon transplantation, SC-NES cells differentiate into neurons and glial cells and extend lond-distance axons, whereas NCX-NES cells remain undifferentiated and display poor integration properties. SC-NES cell upregulate genes related to neurogenesis. In particular. we emphasize the upregulation of MTURN (maturin), ATCAY, PTN (pleiotropin), KAL1 (anosmin), SYT4 and SYT13.
Project description:The transcriptome of single long-term self-renewing neuroepithelial-like stem cells (LT-NES) was studied in order to establish a baseline for investigations into modules of synergistically active transcription factors that determine developmental cell subpopulations