Yang Ruifeng, Zheng Ying, Li Ling, Liu Shujing, Burrows Michelle, Wei Zhi, Nace Arben, Herlyn Meenhard, Cui Rutao, Guo Wei, Cotsarelis George, Xu Xiaowei
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Department of Dermatology, Kligman Laboratories, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Nat Commun. 2014 Dec 16;5:5807. doi: 10.1038/ncomms6807.
Direct reprogramming provides a fundamentally new approach for the generation of patient-specific cells. Here, by screening a pool of candidate transcription factors, we identify that a combination of the three factors, MITF, SOX10 and PAX3, directly converts mouse and human fibroblasts to functional melanocytes. Induced melanocytes (iMels) activate melanocyte-specific networks, express components of pigment production and delivery system and produce melanosomes. Human iMels properly integrate into the dermal-epidermal junction and produce and deliver melanin pigment to surrounding keratinocytes in a 3D organotypic skin reconstruct. Human iMels generate pigmented epidermis and hair follicles in skin reconstitution assays in vivo. The generation of iMels has important implications for studies of melanocyte lineage commitment, pigmentation disorders and cell replacement therapies.
直接重编程为生成患者特异性细胞提供了一种全新的方法。在此，通过筛选一组候选转录因子，我们确定MITF、SOX10和PAX3这三种因子的组合可直接将小鼠和人类成纤维细胞转化为功能性黑素细胞。诱导产生的黑素细胞（iMels）激活黑素细胞特异性网络，表达色素生成和传递系统的成分并产生黑素小体。人类iMels可正确整合到真皮-表皮交界处，并在三维器官型皮肤重建中产生黑色素并将其传递给周围的角质形成细胞。在体内皮肤重建试验中，人类iMels可生成色素沉着的表皮和毛囊。iMels的产生对黑素细胞谱系定向、色素沉着紊乱及细胞替代疗法的研究具有重要意义。
