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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Multilineage-differentiating stress-enduring (Muse) cells are a primary source of induced pluripotent stem cells in human fibroblasts
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Multilineage-differentiating stress-enduring (Muse) cells are a primary source of induced pluripotent stem cells in human fibroblasts

机译：多谱系分化耐力（Muse）细胞是人成纤维细胞中诱导多能干细胞的主要来源

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摘要

The stochastic and elite models have been proposed for the mechanism of induced pluripotent stem (iPS) cell generation. In this study we report a system that supports the elite model. We previously identified multilineage-differentiating stress-endur ing (Muse) cells in human dermal fibroblasts that are character ized by stress tolerance, expression of pluripotency markers, self renewal, and the ability to differentiate into endodermal-, meso dermal-, and ectodermal-lineage cells from a single cell. They can be isolated as stage-specific embryonic antigen-3/CD105 double positive cells. When human fibroblasts were separated into Muse and non-Muse cells and transduced with Oct3/4, Sox2, Klf4, and c-Myc, iPS cells were generated exclusively from Muse cells but not from non-Muse cells. Although some colonies were formed from non-Muse cells, they were unlike iPS cells. Furthermore, epi genetic alterations were not seen, and some of the major pluripo tency markers were not expressed for the entire period during iPS cell generation. These findings were confirmed further using cells transduced with a single polycistronic virus vector encoding all four factors. The results demonstrate that in adult human fibro blasts a subset of preexisting adult stem cells whose properties are similar in some respects to those of iPS cells selectively become iPS cells, but the remaining cells make no contribution to the genera tion of iPS cells. Therefore this system seems to fit the elite model rather than the stochastic model.
机译：已经提出了用于诱导多能干（iPS）细胞生成机制的随机模型和精英模型。在这项研究中，我们报告了支持精英模型的系统。我们先前在人真皮成纤维细胞中鉴定了多系分化性应激耐力（Muse）细胞，其特征在于应激耐受性，多能性标记物的表达，自我更新以及分化为内胚层，中胚层和外胚层的能力。来自单个细胞的谱系细胞。可以将它们分离为阶段特异性胚胎抗原3 / CD105双阳性细胞。当将人类成纤维细胞分为Muse和非Muse细胞并用Oct3 / 4，Sox2，Klf4和c-Myc进行转导时，iPS细胞仅由Muse细胞生成，而不是由非Muse细胞生成。尽管一些集落是由非缪斯细胞形成的，但它们不同于iPS细胞。此外，未见外显子遗传改变，并且在iPS细胞生成的整个过程中，一些主要的多能性标记未表达。使用编码了所有四个因子的单一多顺反子病毒载体转导的细胞进一步证实了这些发现。结果表明，在成年人类成纤维细胞中，某些特性类似于iPS细胞的成年干细胞的一部分选择性地变成了iPS细胞，但其余细胞对iPS细胞的生成没有贡献。因此，该系统似乎适合于精英模型，而不是随机模型。

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