title: MycN Is Critical for the Maintenance of Human Embryonic Stem Cell-Derived Neural Crest Stem Cells.
abstract: The biologic studies of human neural crest stem cells (hNCSCs) are extremely challenging due to the limited source of hNCSCs as well as ethical and technical issues surrounding isolation of early human embryonic tissues. On the other hand, vast majority of studies on MycN have been conducted in human tumor cells, thus, the role of MycN in normal human neural crest development is completely unknown. In the present study, we determined the role of MycN in hNCSCs isolated from in vitro-differentiating human embryonic stem cells (hESCs). For the first time, we show that suppression of MycN in hNCSCs inhibits cell growth and cell cycle progression. Knockdown of MycN in hNCSCs increases the expression of Cdkn1a, Cdkn2a and Cdkn2b, which encodes the cyclin-dependent kinases p21CIP1, p16 INK4a and p15INK4b. In addition, MycN is involved in the regulation of human sympathetic neurogenesis, as knockdown of MycN enhances the expression of key transcription factors involved in sympathetic neuron differentiation, including Phox2a, Phox2b, Mash1, Hand2 and Gata3. We propose that unlimited source of hNCSCs provides an invaluable platform for the studies of human neural crest development and diseases.
authors.affiliation: Key Laboratory for Regenerative Medicine, Ministry of Education, Epithelial Cell Biology Research Center, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong SAR, PR China.
authors.forename: Jie Ting
authors.initials: JT
authors.lastname: Zhang
authors.affiliation: Key Laboratory for Regenerative Medicine, Ministry of Education, Epithelial Cell Biology Research Center, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong SAR, PR China.
authors.forename: Zhi Hui
authors.initials: ZH
authors.lastname: Weng
authors.affiliation: Department of Anatomical and Cellular Pathology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, PR China.
authors.forename: Kam Sze
authors.initials: KS
authors.lastname: Tsang
authors.affiliation: Key Laboratory for Regenerative Medicine, Ministry of Education, Epithelial Cell Biology Research Center, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong SAR, PR China.
authors.forename: Lai Ling
authors.initials: LL
authors.lastname: Tsang
authors.affiliation: Key Laboratory for Regenerative Medicine, Ministry of Education, Epithelial Cell Biology Research Center, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong SAR, PR China.|The Chinese University of Hong Kong, Shenzhen Research Institute, Shenzhen, PR China.
authors.forename: Hsiao Chang
authors.initials: HC
authors.lastname: Chan
authors.affiliation: Key Laboratory for Regenerative Medicine, Ministry of Education, Epithelial Cell Biology Research Center, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong SAR, PR China.|The Chinese University of Hong Kong, Shenzhen Research Institute, Shenzhen, PR China.
authors.forename: Xiao Hua
authors.initials: XH
authors.lastname: Jiang
mesh_terms: D002453:Cell Cycle; D002460:Cell Line; D049109:Cell Proliferation; D002478:Cells, Cultured; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D000066449:Human Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D000071447:N-Myc Proto-Oncogene Protein; D009432:Neural Crest / Q000166:cytology* / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D055495:Neurogenesis; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D015513:Oncogene Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins
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