Hagiwara Kunie, Obayashi Takeshi, Sakayori Nobuyuki, Yamanishi Emiko, Hayashi Ryuhei, Osumi Noriko, Nakazawa Toru, Nishida Kohji
Department of Ophthalmology, Tohoku University Graduate School of Medicine, Seiryo-cho, Aoba-ku, Sendai, Japan ; Department of Ophthalmology, Osaka University Graduate School of Medicine, Yamadaoka, Suita, Japan.
Division of Applied Informatics for Human and Life Science, Tohoku University Graduate School of Information Science, Aramaki-Aza-Aoba, Aoba-ku, Sendai, Japan.
PLoS One. 2014 Jan 20;9(1):e84072. doi: 10.1371/journal.pone.0084072. eCollection 2014.
The outstanding differentiation capacities and easier access from adult tissues, cells derived from neural crest cells (NCCs) have fascinated scientists in developmental biology and regenerative medicine. Differentiation potentials of NCCs are known to depend on their originating regions. Here, we report differential molecular features between craniofacial (cNCCs) and trunk (tNCCs) NCCs by analyzing transcription profiles and sphere forming assays of NCCs from P0-Cre/floxed-EGFP mouse embryos. We identified up-regulation of genes linked to carcinogenesis in cNCCs that were not previously reported to be related to NCCs, which was considered to be, an interesting feature in regard with carcinogenic potentials of NCCs such as melanoma and neuroblastoma. Wnt signal related genes were statistically up-regulated in cNCCs, also suggesting potential involvement of cNCCs in carcinogenesis. We also noticed intense expression of mesenchymal and neuronal markers in cNCCs and tNCCs, respectively. Consistent results were obtained from in vitro sphere-forming and differentiation assays. These results were in accordance with previous notion about differential potentials of cNCCs and tNCCs. We thus propose that sorting NCCs from P0-Cre/floxed-EGFP mice might be useful for the basic and translational research of NCCs. Furthermore, these newly-identified genes up-regulated in cNCC would provide helpful information on NC-originating tumors, developmental disorders in NCC derivatives, and potential applications of NCCs in regenerative medicine.
神经嵴细胞(NCCs)来源的细胞具有出色的分化能力,且更容易从成体组织中获取,这吸引了发育生物学和再生医学领域的科学家。已知NCCs的分化潜能取决于其起源区域。在此,我们通过分析P0-Cre/floxed-EGFP小鼠胚胎中NCCs的转录谱和球形成试验,报告了颅面部(cNCCs)和躯干(tNCCs)NCCs之间的差异分子特征。我们在cNCCs中鉴定出与致癌作用相关的基因上调,这些基因此前未被报道与NCCs有关,这被认为是NCCs在黑色素瘤和神经母细胞瘤等致癌潜能方面的一个有趣特征。Wnt信号相关基因在cNCCs中统计学上调,这也表明cNCCs可能参与致癌作用。我们还分别注意到cNCCs和tNCCs中强烈表达间充质和神经元标记物。体外球形成和分化试验获得了一致的结果。这些结果与之前关于cNCCs和tNCCs分化潜能差异的观点一致。因此,我们提出从P0-Cre/floxed-EGFP小鼠中分选NCCs可能对NCCs的基础研究和转化研究有用。此外,这些在cNCCs中上调的新鉴定基因将为神经嵴起源的肿瘤、NCCs衍生物中的发育障碍以及NCCs在再生医学中的潜在应用提供有用信息。