Efficient generation of human iPSCs by a synthetic self-replicative RNA.
Efficient generation of human iPSCs by a synthetic self-replicative RNA.
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DOI:
10.1016/j.stem.2013.06.001
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发表时间:
2013-08-01
期刊:
影响因子:
23.9
通讯作者:
Dowdy, Steven F.
中科院分区:
文献类型:
--
作者:
Yoshioka, Naohisa;Gros, Edwige;Li, Hai-Ri;Kumar, Shantanu;Deacon, Dekker C.;Maron, Cornelia;Muotri, Alysson R.;Chi, Neil C.;Fu, Xiang-Dong;Yu, Benjamin D.;Dowdy, Steven F.
The generation of human induced Pluripotent Stem (iPS) cells holds great promise for development of regenerative medicine therapies to treat a wide range of human diseases. However, the generation of iPS cells in the absence of integrative DNA vectors remains problematic. Here we report a simple, highly reproducible RNA-based iPS generation approach that utilizes a single, synthetic self-replicating VEE-RF RNA replicon that expresses four reprogramming factors, OCT4, KLF4, SOX2 with c-MYC or GLIS1 at consistent high levels prior to regulated RNA degradation. A single VEE-RF RNA transfection into newborn or adult human fibroblasts resulted in efficient generation of iPS cells with all the hallmarks of stem cells, including cell surface markers, global gene expression profiles and in vivo pluripotency to differentiate into all three germ layers. The VEE-RF RNA-based approach has broad applicability for the generation of iPS cells for ultimate use in human stem cell therapies in regenerative medicine.
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