The role of MYCN in neural crest stem cells
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AbstractHuman embryonic stem cells (hESC) hold great promise for regenerative medicine and therapeutics. Neural crest (NC) cells are multi-potent, migratory, tissue-invasive cells originate in the ectoderm of vertebrate embryos and play a central role in the vertebrate body plan. Neuroblastoma is a common childhood malignant tumour of NC origin, arising in the sympathetic nervous system. Amplification of the oncogene N-Myc is strongly associated with highly malignant behaviour and poor prognosis. Transgenic mice with targeted expression of human N-Myc in NC-derived cells develop neuroblastomas, demonstrating N-Myc over-expression can be an initiating event in neuroblastoma pathogenesis. We hypothesize the pathogenesis of neuroblastoma involves genetic alterations of N-Myc that disrupt embedded NC developmental programs.

In our study, we demonstrate that N-Myc plays critical roles in the maintenance of hESC-derived hNCSCs. N-Myc Knockdown by shRNA in hNCSCs inhibits cell growth and cell cycle progression. Human sympathetic neurogenesis is also promoted by N-Myc suppression. Contrarily, N-Myc overexpression disrupts the normal differentiation of hNCSCs. Compared to control hNCSCs, the N-Myc overexpressing cells exhibited much smaller size. MTT test revealed that N-Myc overexpression promoted cell growth in comparison to control cells. Cell cycle analysis showed increased number of cells was deposited in S-phase in N-Myc overexpression group. Colony formation assay and sphere formation assay indicated that N-Myc overexpressing-cells gained enhanced capacity in self-renewal and proliferation. Soft agar colony formation assay also showed that N-Myc overexpression NCSC could transformed into tumor like cells in vitro. Moreover, our flow data showed the reduction of p75+ cell after N-Myc overexpression, suggesting its inhibitory effect on hNCSC identity.

We demonstrate that aberrant overexpression of N-Myc promotes both anchorage dependent and independent growth of hNCSCs. Altogether, it is plausible that the ectopic overexpression of N-Myc initiates the transition process from hNCSCs to a neuroblastoma-like cells, which warrants further investigation.
All Author(s) ListZhihui WENG
Name of ConferenceFrontiers in Life Sciences, Epithelial Cell Biology Basic and Translational Research
Start Date of Conference20/07/2017
End Date of Conference22/07/2017
Place of ConferenceGuangzhou
Country/Region of ConferenceChina
LanguagesEnglish-United Kingdom

Last updated on 2018-23-01 at 02:47