Adult mice generated from induced pluripotent stem cells
Adult mice generated from induced pluripotent stem cells
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DOI：
10.1038/nature08310
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发表时间：
2009-09-03
期刊：
影响因子：
64.8
通讯作者：
Baldwin, Kristin K.
中科院分区：
文献类型：
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作者：
Boland, Michael J.;Hazen, Jennifer L.;Baldwin, Kristin K.
最近具有里程碑意义的实验表明，少量转录因子的瞬时过度表达可以将分化细胞重编程为类似于胚胎干 (ES) 细胞的诱导多能干 (iPS) 细胞 (1-7)。这些 iPS 细胞在医学上有着巨大的前景，因为它们有潜力产生用于细胞替代疗法的患者特异性细胞类型，并产生体外疾病模型，而无需胚胎组织或卵母细胞 (8-10)。尽管当前的 iPS 细胞系类似于 ES 细胞，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最严格的多能性测试 (3,11)，这引发了关于它们是否足以生成生物体中所有细胞类型的问题。 iPS 和 ES 细胞之间的这种差异是否反映了直接重编程的内在局限性尚不清楚。在这里，我们报道了完全源自 iPS 细胞的可育成年小鼠，这些 iPS 细胞是我们通过小鼠胚胎成纤维细胞的诱导性基因重编程产生的。完全由重新编程的成纤维细胞产生的成年小鼠表明，分化细胞的所有特征都可以恢复到胚胎水平的多能性，而无需暴露于未知的卵质因子。将这些完全多能 iPS 细胞系与发育能力较低的细胞系进行比较，可能会揭示不同多能状态的分子标记。此外，完全源自 iPS 细胞的小鼠将为评估源自 iPS 细胞的细胞和组织的功能和基因组稳定性提供新的资源，这对于验证它们在细胞替代疗法和研究应用中的效用非常重要。
Recent landmark experiments have shown that transient overexpression of a small number of transcription factors can reprogram differentiated cells into induced pluripotent stem (iPS) cells that resemble embryonic stem (ES) cells(1-7). 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(8-10). 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(3,11), 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.