Novel Technique for Inducing Neural Crest Fate in Embryonic Stem Cells (Stem Cells 2009;27:2896-2905)

Abstract

Hotta et al1 has reported a study entitled Small-molecule induction of neural crest-like cells derived from human neural progenitors in the December 2009 issue of Stem Cells. Neural crest (NC) cells are ectoderm-derived multipotent migratory cells that give rise to diverse cell lineages in a developing embryo. Migratory or proliferative deficit of NC cells results in many developmental disorders. Stem cell-based therapies are potential treatment options for such disorders. The enteric nervous system (ENS) of vertebrates predominantly develops from NC cells originating from the vagal end of the neural tube. In Hirschsprung's disease, the distal bowel lacks an ENS caused by a failure of colonization by NC-derived cells. This study shows a simple method of coculture with mouse embryonic fibroblasts (mEFs) for generating NC-like cells from human embryonic stem cells (hESCs). The authors also demonstrated that subsequent exposure to Y27632, a selective inhibitor of the Rho-associated coiled kinase (ROCK), significantly increased the efficiency of differentiation into NC-like cells. These hESC-derived NC-like cells expressed NC markers including p75 (p75NTR low affinity neurotrophin receptor), SoxE (Sox8, Sox9 and Sox10) and HNK1 (human natural killer-1 antigen). The mEFs induced NC-like cells were also able to migrate along NC pathways in avian embryos and differentiate into cells expressing neuronal and glial markers. The hESC-derived NC-like cells also demonstrated migration in mouse gut explants, however, Y27632 treatment was required for differentiation into neuronal and glial cells.