Induced Pluripotent Stem Cells Generated from P0-Cre;Z/EG Transgenic Mice

Neural crest (NC) cells are a migratory, multipotent cell population that arises at the neural plate border, and migrate from the dorsal neural tube to their target tissues, where they differentiate into various cell types. Abnormal development of NC cells can result in severe congenital birth defects. Because only a limited number of cells can be obtained from an embryo, mechanistic studies are difficult to perform with directly isolated NC cells. Protein zero (P0) is expressed by migrating NC cells during the early embryonic period. In the P0-Cre;Z/EG transgenic mouse, transient activation of the P0 promoter induces Cre-mediated recombination, indelibly tagging NC-derived cells with enhanced green fluorescent protein (EGFP). Induced pluripotent stem cell (iPSC) technology offers new opportunities for both mechanistic studies and development of stem cell-based therapies. Here, we report the generation of iPSCs from the P0-Cre;Z/EG mouse. P0-Cre;Z/EG mouse-derived iPSCs (P/G-iPSCs) exhibited pluripotent stem cell properties. In lineage-directed differentiation studies, P/G-iPSCs were efficiently differentiated along the neural lineage while expressing EGFP. These results suggest that P/G-iPSCs are useful to study NC development and NC-associated diseases.神经嵴（Neural crest, NC）细胞是一类迁移性多能细胞群，起源于神经板边界，从背侧神经管迁移至靶组织并在此分化为多种细胞类型。神经嵴细胞发育异常可引发严重的先天性出生缺陷。由于从胚胎中可获取的神经嵴细胞数量有限，直接分离得到的神经嵴细胞难以开展机制研究。蛋白零（Protein zero, P0）在胚胎早期由迁移中的神经嵴细胞表达。在P0-Cre;Z/EG转基因小鼠中，P0启动子的瞬时激活可诱导Cre介导的重组反应，通过增强型绿色荧光蛋白（enhanced green fluorescent protein, EGFP）对神经嵴来源的细胞进行永久标记。诱导多能干细胞（induced pluripotent stem cell, iPSC）技术为机制研究以及基于干细胞的治疗手段开发提供了全新契机。本研究报道了从P0-Cre;Z/EG小鼠中诱导生成诱导多能干细胞的过程：P0-Cre;Z/EG小鼠来源的诱导多能干细胞（以下简称P/G-iPSCs）具备多能干细胞特性。在谱系定向分化实验中，P/G-iPSCs可高效分化为神经谱系细胞，且持续表达EGFP。上述结果表明，P/G-iPSCs可用于神经嵴发育及神经嵴相关疾病的研究。