Recapitulation of Neural Crest Specification and EMT via Induction from Neural Plate Border-like Cells

Summary 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.
Highlights • Human neural plate border-like cells (NBCs) emerge during the E6 neural induction • NBC-to-NCC induction recapitulates sequential steps of NCC specification and EMT • This approach provides a human cell model of early NCC development
Kobayashi et al. show that neural conversion of hiPSCs produces NPB-like cells that can be efficiently converted into NCCs. This enables observation and recapitulation of sequential molecular and cellular events involved in NC specification and EMT, and provides an in vitro platform for investigating human early NCC development and associated disorders.