Generation of human melanocytes from induced pluripotent stem cells.
Generation of human melanocytes from induced pluripotent stem cells.
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DOI：
10.1371/journal.pone.0016182
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发表时间：
2011-01-13
期刊：
影响因子：
3.7
通讯作者：
Kawakami Y
中科院分区：
文献类型：
--
作者：
Ohta S;Imaizumi Y;Okada Y;Akamatsu W;Kuwahara R;Ohyama M;Amagai M;Matsuzaki Y;Yamanaka S;Okano H;Kawakami Y
表皮黑素细胞在保护皮肤免受紫外线照射方面起着重要作用，其功能受损导致色素障碍。此外，黑色素瘤被认为是由黑色素细胞干细胞中积累的突变引起的。然而，人类黑素细胞分化的机制和黑素细胞干细胞的定义特征在很大程度上是未知的。在本研究中，我们着手从人iPS细胞在体外产生黑素细胞，导致人类黑素细胞分化的机制的初步调查。我们使用Yamanaka因子（SOX 2、OCT 3/4和KLF 4，有或没有c-MYC）从人真皮成纤维细胞产生iPS细胞系。这些iPS细胞系随后用于形成胚状体（EB），然后通过补充Wnt 3a、SCF和ET-3的培养物分化成黑素细胞。诱导分化7周后，检测到表达黑素细胞标记物如MITF、酪氨酸酶、SILV和TYRP 1的色素细胞。通过电子显微镜在这些色素细胞中鉴定出黑素体，并且色素细胞的全局基因表达谱显示出与人原代包皮衍生的黑素细胞的高度相似性，这表明从iPS细胞成功生成黑素细胞。这种体外分化系统将有助于了解人类黑素细胞的生物学和揭示各种色素细胞疾病，包括黑色素瘤的机制。
Epidermal melanocytes play an important role in protecting the skin from UV rays, and their functional impairment results in pigment disorders. Additionally, melanomas are considered to arise from mutations that accumulate in melanocyte stem cells. The mechanisms underlying melanocyte differentiation and the defining characteristics of melanocyte stem cells in humans are, however, largely unknown. In the present study, we set out to generate melanocytes from human iPS cells in vitro, leading to a preliminary investigation of the mechanisms of human melanocyte differentiation. We generated iPS cell lines from human dermal fibroblasts using the Yamanaka factors (SOX2, OCT3/4, and KLF4, with or without c-MYC). These iPS cell lines were subsequently used to form embryoid bodies (EBs) and then differentiated into melanocytes via culture supplementation with Wnt3a, SCF, and ET-3. Seven weeks after inducing differentiation, pigmented cells expressing melanocyte markers such as MITF, tyrosinase, SILV, and TYRP1, were detected. Melanosomes were identified in these pigmented cells by electron microscopy, and global gene expression profiling of the pigmented cells showed a high similarity to that of human primary foreskin-derived melanocytes, suggesting the successful generation of melanocytes from iPS cells. This in vitro differentiation system should prove useful for understanding human melanocyte biology and revealing the mechanism of various pigment cell disorders, including melanoma.
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影响因子：
8.4
作者：
Monzani, Elena;Facchetti, Floriana;La Porta, Caterina A. M.
通讯作者：
La Porta, Caterina A. M.
DOI：
10.1073/pnas.0501263102
发表时间：
2005-04-12
影响因子：
11.1
作者：
Amoh, Y;Li, L;Hoffman, RM
通讯作者：
Hoffman, RM
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：
46.9
作者：
Chambers, Stuart M.;Fasano, Christopher A.;Papapetrou, Eirini P.;Tomishima, Mark;Sadelain, Michel;Studer, Lorenz
通讯作者：
Studer, Lorenz
影响因子：
56.9
作者：
Nishimura, EK;Granter, SR;Fisher, DE
通讯作者：
Fisher, DE