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Cell Stem Cell. 2014 Oct 2;15(4):497-506. doi: 10.1016/j.stem.2014.07.013. Epub 2014 Aug 21.

Generation of multipotent induced neural crest by direct reprogramming of human postnatal fibroblasts with a single transcription factor.

Author information

1
Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
2
Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
3
The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
4
The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Center for Sensory Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; The Howard Hughes Medical Institute, Baltimore, MD 21205, USA.
5
Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: glee48@jhmi.edu.

Abstract

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.

PMID:
25158936
DOI:
10.1016/j.stem.2014.07.013
[Indexed for MEDLINE]
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