Human Pluripotent Stem Cell-Derived Neural Crest: Recapitulating Embryonic Development

The neural crest is a developmental tissue that arises in the vertebrate ectoderm and is unique for its capacity to differentiate into a wide range of cell types and ability to migrate throughout the developing embryo. Due to the early stage at which it arises during embryonic development and the ethical issues with experimenting on human embryos little is directly known about human neural crest and instead much of what we understand has been gleaned from animal models of vertebrate development. Human pluripotent stem (hPS) cells offer us a tool that we can use to support the knowledge derived from these models by applying it to human cells, but to date the differentiation of hPS cells into neural crest has only been achieved in ill-defined conditions that compromise the efficacy of the model. The work presented here describes the development of a fully defined system for generating neural crest from hPS cells that can be manipulated in a biologically relevant way to produce other ectodermal phenotypes. As such it represents the first fully defined system for pan- ectodermal differentiation of hPS cells that has been described. The response of the cells undergoing this process to known ectodermal morphogens, particularly BMP, is assessed in depth and the neural crest cells are subjected to rigorous transcriptional and functional analysis. In the future this system could be used to investigate multiple aspects of neural crest and ectodermal biology in the human in a way that has not yet been possible and offers support for the knowledge that has already been collected with classic developmental biology approaches.