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Etiology and Pathogenesis
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Stem Cells
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Cell, Article in
Press, Corrected Proof, doi:10.1016/j.cell.2006.07.024, Available
online 10 August 2006
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Abstract |
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Induction of Pluripotent Stem Cells
from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors
Kazutoshi Takahashi 1
and Shinya Yamanaka1, 2,*
1Department of Stem Cell Biology, Institute for Frontier
Medical Sciences, Kyoto University, Kyoto 606-8507, Japan. 2CREST,
Japan Science and Technology Agency, Kawaguchi 332-0012, Japan. --
*Corresponding author. Email: yamanaka@frontier.kyoto-u.ac.jp --
Received 24 April 2006; revised 18 June 2006; accepted 20
July 2006. Published online: August 10, 2006. Available
online 10 August 2006.
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Differentiated cells can be reprogrammed
to an embryonic-like state by transfer of nuclear contents into
oocytes or by fusion with embryonic stem (ES) cells.
Little is known about factors that induce this reprogramming.
Here, we demonstrate induction of pluripotent stem cells from mouse
embryonic or adult fibroblasts by introducing four factors, Oct3/4,
Sox2, c-Myc, and Klf4, under ES cell culture conditions.
Unexpectedly, Nanog was dispensable.
These cells, which we designated iPS (induced pluripotent stem) cells,
exhibit the morphology and growth properties of ES cells and express
ES cell marker genes.
Subcutaneous transplantation of iPS cells into nude mice resulted in
tumors containing a variety of tissues from all three germ
layers.
Following injection into blastocysts, iPS cells contributed to mouse
embryonic development.
These data demonstrate that pluripotent stem cells can be directly
generated from fibroblast cultures by the addition of only a few
defined factors.
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Copyright © 2006 Elsevier B.V. All
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