Cellular and Molecular Oncogenesis Program, The Wistar Institute, Philadelphia, Pennsylvania, USA.
Stem Cells. 2011 Nov;29(11):1752-62. doi: 10.1002/stem.740.
Mouse and human somatic cells can either be reprogrammed to a pluripotent state or converted to another lineage with a combination of transcription factors suggesting that lineage commitment is a reversible process. Here we show that only one factor, the active intracellular form of Notch1, is sufficient to convert mature pigmented epidermal-derived melanocytes into functional multipotent neural crest (NC) stem-like cells. These induced NC stem cells (iNCSCs) proliferate as spheres under stem cell media conditions, re-express NC-related genes, and differentiate into multiple NC-derived mesenchymal and neuronal lineages. Moreover, iNCSCs are highly migratory and functional in vivo. These results demonstrate that mature melanocytes can be reprogrammed toward their primitive NC cell precursors through the activation of a single stem cell-related pathway. Reprogramming of melanocytes to iNCSCs may provide an alternate source of NCSCs for neuroregenerative applications.
鼠和人体细胞既能被重编程为多能状态，也能通过转录因子的组合转化为另一种谱系，这表明谱系决定是一个可逆的过程。在这里，我们表明只有一种因子，即 Notch1 的活性细胞内形式，足以将成熟的色素性表皮衍生的黑素细胞转化为功能性多能神经嵴（NC）干细胞样细胞。这些诱导的 NC 干细胞（iNCSCs）在干细胞培养基条件下以球体形式增殖，重新表达 NC 相关基因，并分化为多种 NC 衍生的间充质和神经元谱系。此外，iNCSCs 在体内具有高度迁移和功能。这些结果表明，成熟的黑素细胞可以通过激活单个干细胞相关途径向其原始 NC 细胞前体重编程。将黑素细胞重编程为 iNCSCs 可能为神经再生应用提供了 NC 干细胞的替代来源。
