Generation of melanocytes from induced pluripotent stem cells.
Generation of melanocytes from induced pluripotent stem cells.
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DOI：
10.1038/jid.2011.242
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发表时间：
2011-12
影响因子：
6.5
通讯作者：
Xu, Xiaowei
中科院分区：
文献类型：
--
作者：
Yang, Ruifeng;Jiang, Min;Kumar, Suresh M.;Xu, Theodore;Wang, Fei;Xiang, Leihong;Xu, Xiaowei
表皮黑素细胞在保护皮肤免受紫外线 (UV) 伤害方面发挥着重要作用，并与多种皮肤疾病有关。在这里，我们开发了一种将诱导多能干细胞（iPSC）分化为黑素细胞的有效方法。我们首先使用携带鼠 Sox2、Oct3/4、cMyc 和 Klf4 的逆转录病毒载体或无病毒的 PiggyBac 转座子载体从成年小鼠尾尖成纤维细胞 (TTF) 生成 iPSC。 TTF 衍生的 iPSC 克隆表现出与小鼠胚胎干 (ES) 细胞相似的形态和生长特性。 iPSC 表达 ES 细胞标记，显示特征性表观遗传变化，并形成具有所有三个胚层的畸胎瘤。 iPSC 用于生成拟胚体 (EB)，然后通过生长因子处理成功分化为黑素细胞。 iPSC 衍生的黑素细胞表达特征性黑素细胞标记并产生黑色素。电子显微镜显示黑素细胞含有成熟的黑素体。我们操纵了 iPSC 分化为黑素细胞的条件，发现 Wnt3a 并不是小鼠黑素细胞分化所必需的。该报告表明，iPSC 可以很容易地产生黑素细胞，为黑素细胞发育生物学和疾病的体外研究提供了强大的资源。通过在没有病毒的情况下诱导 iPSC，可以降低整合诱变的可能性，从而使 iPSC 更适合细胞替代疗法。
Epidermal melanocytes play an important role in protecting skin from ultraviolet (UV) rays, and are implicated in a variety of skin diseases. Here, we developed an efficient method for differentiating induced pluripotent stem cells (iPSCs) into melanocytes. We first generated iPSCs from adult mouse tail-tip fibroblasts (TTFs) using retroviral vectors or virus-free piggyBac transposon vectors carrying murine Sox2, Oct3/4, cMyc and Klf4. The TTF-derived iPSC clones exhibited similar morphology and growth properties as mouse embryonic stem (ES) cells. The iPSCs expressed ES cell markers, displayed characteristic epigenetic changes and formed teratomas with all three germ layers. The iPSCs were used to generate embryoid bodies (EBs) and were then successfully differentiated into melanocytes by treatment with growth factors. The iPSC-derived melanocytes expressed characteristic melanocyte markers and produced melanin pigment. Electron microscopy showed that the melanocytes contained mature melanosomes. We manipulated the conditions used to differentiate iPSCs to melanocytes and discovered that Wnt3a is not required for mouse melanocyte differentiation. This report shows that melanocytes can be readily generated from iPSCs, providing a powerful resource for the in vitro study of melanocyte developmental biology and diseases. By inducing iPSCs without viruses, the possibility of integration mutagenesis is alleviated, providing iPSCs are more compatible for cell replacement therapies.
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影响因子：
64.8
作者：
Itzhaki, Ilanit;Maizels, Leonid;Gepstein, Lior
通讯作者：
Gepstein, Lior
影响因子：
64.5
作者：
Soldner F;Hockemeyer D;Beard C;Gao Q;Bell GW;Cook EG;Hargus G;Blak A;Cooper O;Mitalipova M;Isacson O;Jaenisch R
通讯作者：
Jaenisch R
DOI：
10.1034/j.1600-0749.2003.00032.x
发表时间：
2003-06-01
期刊：
PIGMENT CELL RESEARCH
影响因子：
--
作者：
Alkhateeb, A;Fain, PR;Spritz, RA
通讯作者：
Spritz, RA
影响因子：
14.8
作者：
Lee, Gabsang;Chambers, Stuart M.;Studer, Lorenz
通讯作者：
Studer, Lorenz
影响因子：
11.4
作者：
NISHIKAWA, S;KUSAKABE, M;NISHIKAWA, SI
通讯作者：
NISHIKAWA, SI