Induction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2

被引:969
作者
Danwei Huangfu [1 ]
Osafune, Kenji [1 ,2 ]
Maehr, Rene [1 ]
Guo, Wenjun [3 ]
Eijkelenboom, Astrid [1 ,4 ]
Chen, Shuibing [1 ]
Muhlestein, Whitney [1 ]
Melton, Douglas A. [1 ]
机构
[1] Harvard Univ, Howard Hughes Med Inst, Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA
[2] Japan Sci & Technol Agcy, ICORP Organ Regenerat Project, Meguro Ku, Tokyo 1538902, Japan
[3] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA
[4] Univ Utrecht, NL-3508 TC Utrecht, Netherlands
关键词
D O I
10.1038/nbt.1502
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Ectopic expression of defined sets of genetic factors can reprogram somatic cells to induced pluripotent stem (iPS) cells that closely resemble embryonic stem (ES) cells. The low efficiency with which iPS cells are derived hinders studies on the molecular mechanism of reprogramming, and integration of viral transgenes, in particular the oncogenes c-Myc and Klf4, may handicap this method for human therapeutic applications. Here we report that valproic acid (VPA), a histone deacetylase inhibitor, enables reprogramming of primary human fibroblasts with only two factors, Oct4 and Sox2, without the need for the oncogenes c-Myc or Klf4. The two factor-induced human iPS cells resemble human ES cells in pluripotency, global gene expression profiles and epigenetic states. These results support the possibility of reprogramming through purely chemical means, which would make therapeutic use of reprogrammed cells safer and more practical.
引用
收藏
页码:1269 / 1275
页数:7
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