Yong Jun Kim,1,2 Hotae Lim,1 Zhe Li,3 Yohan Oh,1,2 Irina Kovlyagina,1 In Young Choi,1 Xinzhong Dong,3,4,5and Gabsang Lee1,2,3,*
1Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
2Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
3The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
4Center for Sensory Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
5The Howard Hughes Medical Institute, Baltimore, MD 21205, USA
*Correspondence
SUMMARY
Neural crest (NC) generates diverse lineages including peripheral neurons, glia, melanocytes, and mesenchymal derivatives. Isolating multipotent human NC has proven challenging, limiting our ability to understand NC development and model NC-associated disorders. Here, we report direct reprogramming of human fibroblasts into induced neural crest (iNC) cells by overexpression of a single transcription factor, SOX10, in combination with environmental cues including WNT activation. iNC cells possess extensive capacity for migration in vivo, and single iNC clones can differentiate into the four main NC lineages. We further identified a cell surface marker for prospective isolation of iNCs, which was used to generate and purify iNCs from familial dysautonomia (FD) patient fibroblasts. FD-iNC cells displayed defects in cellular migration and alternative mRNA splicing, providing insights into FD pathogenesis. Thus, this study provides an accessible platform for studying NC biology and disease through rapid and efficient reprogramming of human postnatal fibroblasts.