Neural crest cells (NCCs) contribute to several tissues during embryonic development. NCC formation depends on activation of tightly regulated molecular programs at the neural plate border (NPB) region, which initiate NCC specification and epithelial-to-mesenchymal transition (EMT). Although several approaches to investigate NCCs have been devised, these early events of NCC formation remain largely unknown in humans, and currently available cellular models have not investigated EMT. Here, we report that the E6 neural induction protocol converts human induced pluripotent stem cells into NPB-like cells (NBCs), from which NCCs can be efficiently derived. NBC-to-NCC induction recapitulates gene expression dynamics associated with NCC specification and EMT, including downregulation of NPB factors and upregulation of NCC specifiers, coupled with other EMT-associated cell-state changes, such as cadherin modulation and activation of TWIST1 and other EMT inducers. This strategy will be useful in future basic or translational research focusing on these early steps of NCC formation.

神经c细胞（NCC）在胚胎发育过程中有助于多种组织。NCC的形成取决于神经板边界（NPB）区域受严格调控的分子程序的激活，从而启动NCC规范和上皮-间充质转化（EMT）。尽管已经设计了几种研究NCC的方法，但是这些NCC形成的早期事件在人类中仍然是未知的，并且当前可用的细胞模型尚未研究EMT。在这里，我们报道E6神经诱导协议将人类诱导的多能干细胞转换为NPB样细胞（NBCs），可以从中有效地提取NCC。从NBC到NCC的诱导概括了与NCC规范和EMT相关的基因表达动力学，包括NPB因子的下调和NCC指示剂的上调，加上其他与EMT相关的细胞状态变化，例如钙黏着蛋白调制和TWIST1和其他EMT诱导物的激活。该策略将在未来的基础或转化研究中有用，这些研究关注NCC形成的这些早期步骤。