RRC ID 63418
Author Zhang JT, Weng ZH, Tsang KS, Tsang LL, Chan HC, Jiang XH.
Title MycN Is Critical for the Maintenance of Human Embryonic Stem Cell-Derived Neural Crest Stem Cells.
Journal PLoS One
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.
Volume 11(1)
Pages e0148062
Published 2016-1-1
DOI 10.1371/journal.pone.0148062
PII PONE-D-15-06720
PMID 26815535
PMC PMC4729679
MeSH Cell Cycle Cell Line Cell Proliferation* Cells, Cultured Gene Expression Regulation, Developmental Gene Knockdown Techniques Human Embryonic Stem Cells / cytology* Human Embryonic Stem Cells / metabolism Humans N-Myc Proto-Oncogene Protein Neural Crest / cytology* Neural Crest / metabolism Neural Stem Cells / cytology* Neural Stem Cells / metabolism Neurogenesis* Nuclear Proteins / genetics* Nuclear Proteins / metabolism Oncogene Proteins / genetics* Oncogene Proteins / metabolism
IF 2.74
Human and Animal Cells MC3T3-G2/PA6(RCB1127)