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.
Highlights
The neural crest originates in the ectodermal layer of developing vertebrate embryos
To further identify populations of human neural crest stem cells (hNCSCs) within differentiating human embryonic stem cells (hESCs) cultures, we evaluated the expression of neural crest stem cells (NCSCs) markers by immunostaining and FACS analysis
We have shown that knockdown of MycN inhibits cell proliferation in hNCSCs
Summary
The neural crest originates in the ectodermal layer of developing vertebrate embryos. Through a series of highly orchestrated molecular signals, neuro-ectodermal cells are induced to first create neural crest stem cells (NCSCs). NCSCs respond to a variety of differentiation and migration signals to produce terminally differentiated neural crest (NC) derivatives including sympathetic and parasympathetic ganglia, adrenal medulla, connective tissues, and an array of different cell types [1]. At each step of this process, stage-and cell type-specific gene. MycN in Human Neural Crest Stem Cells expression ensures successful tissue development. Disruption of this gene expression cascade at any point leads to aberrant proliferation, apoptosis, and/or differentiation
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
