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Induced pluripotent stem (iPS) cells

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Suppression of induced pluripotent stem cell generation by the p53 p21 pathway Hyenjong Hong, Kazutoshi Takahashi, Tomoko Ichisaka, Takashi Aoi, ... – PowerPoint PPT presentation

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Title: Induced pluripotent stem (iPS) cells


1
Induced pluripotent stem (iPS)cells
  • Patient-Specific Pluripotent Stem Cells

2
Nuclear reprogramming to a pluripotent state by
three approachesShinya Yamanaka Helen M.
BlauNATUREVol 46510 June 2010doi10.1038/natur
e09229
3
The fusion experiments by Tada, Surani and
colleagues clearly showed that ES cells and
embryonic germ cells contain factors that can
induce reprogramming and pluripotency in somatic
cells. Before 2006, the prevailing view was
that nuclear reprogramming to a pluripotent state
is a highly complex process that might entail the
cooperation of up to 100 factors.
Tada, M., Tada, T., Lefebvre, L., Barton, S. C.
Surani, M. A. Embryonic germ cells induce
epigenetic reprogramming of somatic nucleus in
hybrid cells. EMBO J. 16, 65106520 (1997).
Nuclear reprogramming to a pluripotent state
by three approachesShinya Yamanaka Helen M.
BlauNATUREVol 46510 June 2010doi10.1038/natur
e09229
4
Nuclear reprogramming to a pluripotent state by
three approachesShinya Yamanaka Helen M.
BlauNATUREVol 46510 June 2010doi10.1038/natur
e09229
5
Induction of Pluripotent Stem Cells from Mouse
Embryonic and AdultFibroblast Cultures by
Defined FactorsKazutoshi Takahashi and Shinya
YamanakaCell 126, 663676, August 25, 2006
b-geo cassette (a fusion of the
b-galactosidase and neomycin resistance genes)
24 genes
Oct3/4, Klf4, Sox2, and c-Myc
Morphology 5/12 survived
6
Induction of Pluripotent Stem Cells from Mouse
Embryonic and AdultFibroblast Cultures by
Defined FactorsKazutoshi Takahashi and Shinya
YamanakaCell 126, 663676, August 25, 2006
7
Gene-Expression Profiles of iPS Cells
Induction of Pluripotent Stem Cells from Mouse
Embryonic and Adult Fibroblast Cultures by
Defined FactorsKazutoshi Takahashi and Shinya
YamanakaCell 126, 663676, August 25, 2006
8
Pluripotency of iPS Cells Derived from MEFs
they are different with regards to gene
expression and DNA methylation patterns, and fail
to produce adult chimaeras.
Induction of Pluripotent Stem Cells from Mouse
Embryonic and Adult Fibroblast Cultures by
Defined FactorsKazutoshi Takahashi and Shinya
YamanakaCell 126, 663676, August 25, 2006
9
Generation of germline-competent induced
pluripotent stem cells Keisuke Okita, Tomoko
Ichisaka Shinya Yamanaka Vol 448 19 July 2007
doi10.1038/nature05934
10
The generation of iPS cells from adult human
dermal fibroblasts with the same four factors
Oct3/4, Sox2, Klf4, and c-Myc. Human iPS cells
were similar to human embryonic stem (ES) cells
in morphology, proliferation, surface antigens,
gene expression, epigenetic status of pluripotent
cell-specific genes, and telomerase activity.
Furthermore, these cells could differentiate into
cell types of the three germ layers in vitro and
in teratomas. These findings demonstrate that
iPS cells can be generated from adult human
fibroblasts.
Induction of Pluripotent Stem Cells from Adult
Human Fibroblasts by Defined Factors Kazutoshi
Takahashi, Koji Tanabe, Mari Ohnuki, Megumi
Narita, Tomoko Ichisaka, Kiichiro Tomoda, and
Shinya Yamanaka1,2
11
Up to 10 of transduced mouse embryonic
fibroblasts lacking p53 became iPS cells, even
without the Myc retrovirus. The p53 deletion also
promoted the induction of integration-free mouse
iPS cells with plasmid transfection.
Furthermore, in the p53-null background, iPS
cells were generated from terminally
differentiated T lymphocytes. The suppression of
p53 also increased the efficiency of humaniPS
cell generation.
Suppression of induced pluripotent stem cell
generation by the p53p21 pathway Hyenjong Hong,
Kazutoshi Takahashi, Tomoko Ichisaka, Takashi
Aoi, Osami Kanagawa, Masato Nakagawa, Keisuke
Okita Shinya Yamanaka Vol 46027 August 2009
doi10.1038/nature08235
12
Nuclear reprogramming to a pluripotent state by
three approachesShinya Yamanaka Helen M.
BlauNATUREVol 46510 June 2010doi10.1038/natur
e09229
13
Timeline of discoveries in nuclear reprogramming.
Nuclear reprogramming to a pluripotent state by
three approachesShinya Yamanaka Helen M.
BlauNATUREVol 46510 June 2010doi10.1038/natur
e09229
14
Shinya Yamanaka, Professor of Kyoto University,
won the Albert Lasker Basic Medical Research
Award in 2009.
Often referred to as Americas Nobel, the
Lasker Award is one of the most prestigious
scientific awards.
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