Induction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2
被引:969
作者:
Danwei Huangfu
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Harvard Univ, Howard Hughes Med Inst, Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USAHarvard Univ, Howard Hughes Med Inst, Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA
Danwei Huangfu
[1
]
Osafune, Kenji
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机构:
Harvard Univ, Howard Hughes Med Inst, Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA
Japan Sci & Technol Agcy, ICORP Organ Regenerat Project, Meguro Ku, Tokyo 1538902, JapanHarvard Univ, Howard Hughes Med Inst, Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA
Osafune, Kenji
[1
,2
]
Maehr, Rene
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机构:
Harvard Univ, Howard Hughes Med Inst, Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USAHarvard Univ, Howard Hughes Med Inst, Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA
Maehr, Rene
[1
]
Guo, Wenjun
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机构:
Whitehead Inst Biomed Res, Cambridge, MA 02142 USAHarvard Univ, Howard Hughes Med Inst, Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA
Guo, Wenjun
[3
]
Eijkelenboom, Astrid
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机构:
Harvard Univ, Howard Hughes Med Inst, Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA
Univ Utrecht, NL-3508 TC Utrecht, NetherlandsHarvard Univ, Howard Hughes Med Inst, Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA
Eijkelenboom, Astrid
[1
,4
]
Chen, Shuibing
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机构:
Harvard Univ, Howard Hughes Med Inst, Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USAHarvard Univ, Howard Hughes Med Inst, Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA
Chen, Shuibing
[1
]
Muhlestein, Whitney
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机构:
Harvard Univ, Howard Hughes Med Inst, Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USAHarvard Univ, Howard Hughes Med Inst, Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA
Muhlestein, Whitney
[1
]
Melton, Douglas A.
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Harvard Univ, Howard Hughes Med Inst, Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USAHarvard Univ, Howard Hughes Med Inst, Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA
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
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.
机构:
Natl Res Council Canada, Inst Biol Sci, Neurobiol Program, Ottawa, ON K1A 0R6, CanadaNatl Res Council Canada, Inst Biol Sci, Neurobiol Program, Ottawa, ON K1A 0R6, Canada
Deb-Rinker, P
Ly, D
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Natl Res Council Canada, Inst Biol Sci, Neurobiol Program, Ottawa, ON K1A 0R6, CanadaNatl Res Council Canada, Inst Biol Sci, Neurobiol Program, Ottawa, ON K1A 0R6, Canada
Ly, D
Jezierski, A
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Natl Res Council Canada, Inst Biol Sci, Neurobiol Program, Ottawa, ON K1A 0R6, CanadaNatl Res Council Canada, Inst Biol Sci, Neurobiol Program, Ottawa, ON K1A 0R6, Canada
Jezierski, A
Sikorska, M
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Natl Res Council Canada, Inst Biol Sci, Neurobiol Program, Ottawa, ON K1A 0R6, CanadaNatl Res Council Canada, Inst Biol Sci, Neurobiol Program, Ottawa, ON K1A 0R6, Canada
Sikorska, M
Walker, PR
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机构:
Natl Res Council Canada, Inst Biol Sci, Neurobiol Program, Ottawa, ON K1A 0R6, CanadaNatl Res Council Canada, Inst Biol Sci, Neurobiol Program, Ottawa, ON K1A 0R6, Canada
机构:
Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA
Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA
Free Univ Berlin, Dept Biol Chem & Pharm, D-1000 Berlin, GermanyMassachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA
Eminli, Sarah
Utikal, Jochen
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机构:
Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA
Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USAMassachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA
Utikal, Jochen
Arnold, Katrin
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机构:
Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA
Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USAMassachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA
Arnold, Katrin
Jaenisch, Rudolf
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机构:
MIT, Dept Biol, Cambridge, MA USA
MIT, Whitehead Inst, Cambridge, MA USAMassachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA
Jaenisch, Rudolf
Hochedlinger, Konrad
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机构:
Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA
Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USAMassachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA
机构:
Natl Res Council Canada, Inst Biol Sci, Neurobiol Program, Ottawa, ON K1A 0R6, CanadaNatl Res Council Canada, Inst Biol Sci, Neurobiol Program, Ottawa, ON K1A 0R6, Canada
Deb-Rinker, P
Ly, D
论文数: 0引用数: 0
h-index: 0
机构:
Natl Res Council Canada, Inst Biol Sci, Neurobiol Program, Ottawa, ON K1A 0R6, CanadaNatl Res Council Canada, Inst Biol Sci, Neurobiol Program, Ottawa, ON K1A 0R6, Canada
Ly, D
Jezierski, A
论文数: 0引用数: 0
h-index: 0
机构:
Natl Res Council Canada, Inst Biol Sci, Neurobiol Program, Ottawa, ON K1A 0R6, CanadaNatl Res Council Canada, Inst Biol Sci, Neurobiol Program, Ottawa, ON K1A 0R6, Canada
Jezierski, A
Sikorska, M
论文数: 0引用数: 0
h-index: 0
机构:
Natl Res Council Canada, Inst Biol Sci, Neurobiol Program, Ottawa, ON K1A 0R6, CanadaNatl Res Council Canada, Inst Biol Sci, Neurobiol Program, Ottawa, ON K1A 0R6, Canada
Sikorska, M
Walker, PR
论文数: 0引用数: 0
h-index: 0
机构:
Natl Res Council Canada, Inst Biol Sci, Neurobiol Program, Ottawa, ON K1A 0R6, CanadaNatl Res Council Canada, Inst Biol Sci, Neurobiol Program, Ottawa, ON K1A 0R6, Canada
机构:
Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA
Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA
Free Univ Berlin, Dept Biol Chem & Pharm, D-1000 Berlin, GermanyMassachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA
Eminli, Sarah
Utikal, Jochen
论文数: 0引用数: 0
h-index: 0
机构:
Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA
Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USAMassachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA
Utikal, Jochen
Arnold, Katrin
论文数: 0引用数: 0
h-index: 0
机构:
Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA
Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USAMassachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA
Arnold, Katrin
Jaenisch, Rudolf
论文数: 0引用数: 0
h-index: 0
机构:
MIT, Dept Biol, Cambridge, MA USA
MIT, Whitehead Inst, Cambridge, MA USAMassachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA
Jaenisch, Rudolf
Hochedlinger, Konrad
论文数: 0引用数: 0
h-index: 0
机构:
Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA
Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USAMassachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA