Generation of Multipotent Induced Neural Crest by Direct Reprogramming of Human Postnatal Fibroblasts with a Single Transcription Factor
- Authors
- Kim, Yong Jun; Lim, Hotae; Li, Zhe; Oh, Yohan; Kovlyagina, Iri; Choi, In Young; Dong, Xinzhong; Lee, Gabsang
- Issue Date
- Oct-2014
- Publisher
- CELL PRESS
- Citation
- CELL STEM CELL, v.15, no.4, pp.497 - 506
- Indexed
- SCIE
SCOPUS
- Journal Title
- CELL STEM CELL
- Volume
- 15
- Number
- 4
- Start Page
- 497
- End Page
- 506
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/158883
- DOI
- 10.1016/j.stem.2014.07.013
- ISSN
- 1934-5909
- 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 fourmain 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.
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