Dedifferentiation of human terminally differentiating keratinocytes into their precursor cells induced by basic fibroblast growth factor.
Dedifferentiation of human terminally differentiating keratinocytes into their precursor cells induced by basic fibroblast growth factor.
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DOI：
10.1248/bpb.34.1037
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发表时间：
2011-07
影响因子：
2
通讯作者：
Xiaoyan Sun;Xiaobing Fu;W. Han;Ya-li Zhao;Hui-ling Liu;Z. Sheng
中科院分区：
文献类型：
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作者：
Xiaoyan Sun;Xiaobing Fu;W. Han;Ya-li Zhao;Hui-ling Liu;Z. Sheng
将分化的细胞重新编程为干细胞可能在干细胞研究和再生医学中有长期的应用。在此，我们报道了人表皮角质形成细胞在体外用碱性成纤维细胞生长因子(BFGF)去分化为其前体细胞，而不是外部基因干预。经终末分化的人角质形成细胞孵育后，部分存活的角质形成细胞从分化状态恢复到去分化状态，天然角质形成干细胞的生物标志物重新表达，包括β(1)-整合素、CK19和CK14。此外，细胞周期分析显示，脱分化来源的KSCs具有较高的集落形成能力，明显聚集在S期，在超微结构水平上获得了α(6)整合素和CD71表达的相似的区域分布，并通过从核仁位置释放端粒酶到核质分布而增强了增殖能力。然而，在比较dKSCs和nKSCs时，有两点值得注意：(1)经bFGF处理的dKSCs中的转运扩增细胞比例明显高于nKSCs；(2)nKSCs和dKSCs中端粒酶的亚细胞定位存在地区差异。大多数nKSCs核仁中人端粒酶逆转录酶的表达明显集中，而大多数dKSCs核内端粒酶的分布较弥漫，甚至核仁上的信号较一般核浆中的信号缺失。这些结果表明，碱性成纤维细胞生长因子可以诱导向终末分化的表皮角质形成细胞转化为前体细胞，为创面修复和再生提供了一种新的途径。
Reprogramming differentiated cells toward stem cells may have long-term applications in stem-cell research and regenerative medicine. Here we report on the dedifferentiation of human epidermal keratinocytes into their precursor cells in vitro with basic fibroblast growth factor (bFGF) but not external gene intervention. After incubation of human terminally differentiating keratinocytes, some of the surviving keratinocytes reverted from a differentiated to a dedifferentiated state, as evidenced by re-expression of biological markers of native keratinocyte stem cells (nKSCs), including β(1)-integrin, CK19 and CK14. Moreover, these dedifferentiation-derived KSCs (dKSCs) showed an ability for high colony formation correlated with cell cycle analysis showing a marked accumulation in S phases, acquired a similar regional distribution of both α(6)-integrin and CD71 expression at the ultrastructural level, and had a increased proliferative capacity by releasing telomerase from nucleolar sites to nucleoplasmic distribution. However, on comparing dKSCs with nKSCs, 2 points seem noteworthy: (1) the proportion of transit amplifying cells in dKSCs treated with bFGF is much higher than that in nKSCs and (2) regional differences exist in the subcellular localization of telomerase in nKSCs and dKSCs. Most nKSCs showed a prominent nucleolar concentration of human telomerase reverse transcriptase expression, whereas most dKSCs showed a more diffuse intranuclear distribution of telomerase or even signal depletion at nucleoli relative to the general nucleoplasm. These results indicate that bFGF could induce the terminally differentiating epidermal keratinocytes to convert into their precursor cells, which offers a new approach for generating residual healthy stem cells for wound repair and regeneration.