oa Comprehensive Transcriptome and Proteome Analysis of Human Embryonic Stem Cells Differentiation to Neural Cells

Human embryonic stem cells (hESCs) are pluripotent cells capable of differentiating into other cell lineages in vivo. Global gene expression analysis of hESCs that differentiate into neural cells would help to further define the molecular mechanisms involved in neurogenesis in humans. We performed a comprehensive transcriptome and proteome analysis of hESC differentiation at three different stages: early neural differentiation, neural ectoderm and differentiated neurons. We identified and validated time-dependent gene expression patterns and showed that the gene expression patterns reflect early ESC differentiation. Sets of genes are induced in primary ectodermal lineages and then in differentiated neurons, constituting consecutive waves of known and novel genes. Pathway analysis revealed dynamic expression patterns of members of several signaling pathways, including NOTCH, mTOR and Toll like receptors (TLR), during neural differentiation. Owing to comparative proteomics and transcriptomics analyses, novel genes involved in proliferation of rosette cells, fate specification and neural differentiation were identified. Functional analysis with RNAi figured up that suppression of a protein involved in mRNA processing, MAGOHB, enhanced the neural differentiation of hESCs. Collectively, these results enhance our understanding of the molecular dynamics underlying neural commitment and differentiation.