Derivation of Induced Neural Crest from Human Postnatal Fibroblasts

Recent direct conversion studies have employed multiple transcription factors to force somatic cells into different cellular fates. Here we report the direct conversion of human fibroblasts into induced neural crest (iNC) with a single genetic factor (SOX10) and environmental cues, including WNT activation. The isolated human iNC population exhibits transcriptional similarity to their hESC-derived counterpart, extensive migration ability and differentiation potentials toward multiple lineages. Furthermore, we identified a cell surface marker to prospectively isolate the iNC population from postnatal fibroblasts, allowing purification of disease-specific iNCs from fibroblasts of familial dysautonomia (FD) patients. Transcriptional characterization of FD-iNCs strongly demonstrated defective migration and alternative splicing, providing new insights into FD disease mechanism. Our studies demonstrate the feasibility of rapid and efficient direct conversion of human postnatal fibroblasts into iNCs with cell intrinsic and extrinsic cues, which could have important implications for studies of neural crest related disorders.