TY - JOUR
T1 - Induction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2
AU - Huangfu, Danwei
AU - Osafune, Kenji
AU - Maehr, René
AU - Guo, Wenjun
AU - Eijkelenboom, Astrid
AU - Chen, Shuibing
AU - Muhlestein, Whitney
AU - Melton, Douglas A.
N1 - Funding Information:
D.A.M. is a Howard Hughes Medical Institute Investigator. D.H. is funded by the Helen Hay Whitney Foundation and Novartis Institutes for BioMedical Research. S.C. is supported by the Juvenile Diabetics Research Foundation. The authors thank Anastasie Kweudjeu for assistance with micoarray analysis, Konrad Hochedlinger for providing probes for Southern blot analysis, Shinya Yamanaka for providing viral vectors through Addgene and Robert Weinberg for support of this study. Some monoclonal antibodies were obtained from the Developmental Studies Hybridoma Bank, which was developed under the auspices of the National Institute of Child Health and Human Development and is maintained by The University of Iowa, Department of Biological Sciences.
PY - 2008/11
Y1 - 2008/11
N2 - 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.
AB - 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.
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U2 - 10.1038/nbt.1502
DO - 10.1038/nbt.1502
M3 - Article
C2 - 18849973
AN - SCOPUS:55749104227
SN - 1087-0156
VL - 26
SP - 1269
EP - 1275
JO - Nature biotechnology
JF - Nature biotechnology
IS - 11
ER -