direct-reprogramming-of-mouse-fibroblasts-into-melanocytes

Direct Reprogramming of Mouse Fibroblasts into Melanocytes

The loss of function of melanocytes leads to vitiligo, which seriously affects the physical and mental health of the affected individuals. Presently, ...

Jiangsu University

Affiliated Hospital of Jiangsu University

Jiangsu university

Induced pluripotent stem cells (iPSCs) are a promising melanocyte source as they propagate indefinitely and can be established from patients. However, the in vivo functions of human iPSC-derived melanocytes (hiMels) remain unknown. Here, we generated hiMels from vitiligo patients using a three-dimensional system with enhanced differentiation efficiency, which showed characteristics of human epidermal melanocytes with high sequence similarity and involved in multiple vitiligo-associated signaling pathways. A modified hair follicle reconstitution assay in vivo showed that MITFPAX3TYRP1 hiMels were localized in the mouse hair bulb and epidermis and produced melanin up to 7 weeks after transplantation, whereas MITFPAX3TYRP1 hiMelanocyte stem cells integrated into the bulge-subbulge regions. Overall, these data demonstrate the long-term functions of hiMels in vivo to reconstitute pigmented hair follicles and to integrate into normal regions for both mature melanocytes and melanocyte stem cells, providing an alternative source of personalized cellular therapy for depigmentation.

Therapeutic Potential of Patient iPSC-Derived iMelanocytes in Autologous Transplantation.

Induced pluripotent stem cells (iPSCs) show huge variations in their differentiation potential, even in the same condition. However, methods for predicting these differentiation tendencies, especially in the early stage of differentiation, are still scarce. This study aimed to establish a simple and practical system to predict the differentiation tendency of iPSC lines using embryoid bodies (EBs) with identified parameters in the early stage. We compared four human iPSC lines in terms of the morphology and maintenance of EBs and their gene expression levels of specific markers for three germ-layers. Furthermore, the differentiation potentials of these iPSC lines into melanocytes, which are ectoderm-derived cells, were also compared and correlated with the above parameters. The results showed that iPSC lines forming regular, smooth, and not cystic EBs, which could be maintained in culture for a relatively longer time, also expressed higher levels of ectoderm-specific markers and lower levels of mesoderm/endoderm markers. Additionally, these iPSC lines showed greater potential in melanocyte differentiation using EB-based protocol, and the induced melanocytes expressed melanocytic markers and presented characteristics that were similar to those of normal human melanocytes. By contrast, iPSC lines that formed cystic EBs with bright or dark cavities and expressed relatively lower levels of ectoderm-specific markers failed in the melanocyte differentiation. Collectively, the differentiation tendency of human iPSC lines may be predicted by specific parameters in the EB stage. The formation and maintenance of optimal EBs and the expression of germ layer-specific markers are particularly important and practical for the prediction assay in the early stage.

Yi-Xuan Zhang

Institute for Regenerative Medicine

Jiangsu University

Direct Reprogramming of Mouse Fibroblasts into Melanocytes

Yi-Xuan Zhang

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Jiangsu University

Direct Reprogramming of Mouse Fibroblasts into Melanocytes

Institute for Regenerative Medicine