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Adult mice generated from induced pluripotent stem cells

机译：从诱导多能干细胞产生的成年小鼠

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摘要

Recent landmark experiments have shown that transient over-expression of a small number of transcription factors can re-program differentiated cells into induced pluripotent stem (iPS) cells that resemble embryonic stem (ES) cells. These iPS cells hold great promise for medicine because they have the potential to generate patient-specific cell types for cell replacement therapy and produce in vitro models of disease, without requiring embryonic tissues or oocytes. Although current iPS cell lines resemble ES cells, they have not passed the most stringent test of pluripotency by generating full-term or adult mice in tetraploid complementation assays, raising questions as to whether they are sufficiently potent to generate all of the cell types in an organism. Whether this difference between iPS and ES cells reflects intrinsic limitations of direct reprogramming is not known. Here we report fertile adult mice derived entirely from iPS cells that we generated by inducible genetic reprogramming of mouse embryonic fibroblasts. Producing adult mice derived entirely from a reprogrammed fibroblast shows that all features of a differentiated cell can be restored to an embryonic level of pluripotency without exposure to unknown ooplasmic factors. Comparing these fully pluripotent iPS cell lines to less developmentally potent lines may reveal molecular markers of different pluripotent states. Furthermore, mice derived entirely from iPS cells will provide a new resource to assess the functional and genomic stability of cells and tissues derived from iPS cells, which is important to validate their utility in cell replacement therapy and research applications.
机译：最近的标志性实验表明，少量转录因子的瞬时过表达可以将分化的细胞重新编程为诱导型多能干（iPS）细胞，类似于胚胎干（ES）细胞。这些iPS细胞在医学上具有广阔的前景，因为它们具有生成特定于患者的细胞类型进行细胞替代疗法并产生体外疾病模型的潜力，而无需胚胎组织或卵母细胞。尽管目前的iPS细胞系与ES细胞相似，但它们尚未通过在四倍体互补测定中生成足月或成年小鼠的多能性试验而通过最严格的测试，这引发了关于它们是否足够有效地在小鼠体内产生所有细胞类型的疑问。生物。目前尚不清楚iPS和ES细胞之间的这种差异是否反映了直接重编程的固有局限性。在这里，我们报道了完全由iPS细胞衍生的可育成年小鼠，我们通过小鼠胚胎成纤维细胞的可诱导遗传重编程生成了iPS细胞。完全衍生自重新编程的成纤维细胞的成年小鼠显示，分化细胞的所有功能都可以恢复到多能性的胚胎水平，而无需暴露于未知的卵质因子。将这些完全多能的iPS细胞系与发育潜能较低的系进行比较，可能会发现不同多能状态的分子标记。此外，完全源自iPS细胞的小鼠将提供新的资源来评估源自iPS细胞的细胞和组织的功能和基因组稳定性，这对于验证其在细胞替代治疗和研究应用中的实用性至关重要。

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  • 来源
    《Nature》 |2009年第7260期|91-94|共4页
  • 作者

    Michael J. Boland; Jennifer L. Hazen; Kristopher L. Nazor; Alberto R. Rodriguez; Wesley Gifford; Greg Martin; Sergey Kupriyanov; Kristin K. Baldwin;

  • 作者单位

    Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA;

    Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA;

    Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA;

    Mouse Genetics Core Facility, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA;

    Medical Scientist Training Program, University of California, San Diego, La Jolla, California 92037, USA;

    Mouse Genetics Core Facility, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA;

    Mouse Genetics Core Facility, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA;

    Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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