1. ATIT- Animal Technology Institute Taiwan
.
;
972004206;
2009/11/9
iPSC
ppt

2. 1970 2001
induced pluripotent stem
cells 2006 Shinya
Yamanaka
protein-induced Pluripotent
Stem Cells 2009
Hongyan Zhou
1962 JB Gurdon Xenopus
2009 iPSC piPSC ”piPSC iPSC”
Xenopus laevis
1962, JB Gurdon 2009, Zhou et al.
egg
1962 John Gurdon nuclear transplant
” ” (egg) nuclear
blastula, gastrula endoderm ” ” transplantation cloning
1950
tadpole (JB Gurdon, 1962) nuclear
transplantation
2009 Albert-
Lasker Basic Medical
Research Award
1962
paper
oct-4
2003 JB Gurdon (thymus) Xenopus
oocytes X. laevis paper Xenopus oocytes oct-4
oocytes oct-4 knockout
oct-4
transcription factor
POU5F1 POU family
2006 Shinya Yamanaka
Oct3/4, Sox2, c-Myc, Klf4 nuclear reprogramming(
) retroviral fibroblast
hES medium
colony iPSC Yamanaka Fbx15 iPSC
2

3. DNA eukaryotic
cell
1. ES cell teratoma
2. DNA methylation Transfection:
3. chimera 1. electroporation
2. calcium phosphate,
4. factor c-Myc oncogene DEAE-dextran cell
DNA
3.Lipofection
2007 Yamanaka iPS cell ES 4.Microinjection(
1962JB Gurdon )
cell Nanog selection marker
Fbx15 DNA methylation chimera Transduction:
retrovirus
Hongyan Zhou recombinant protein piPSC reverse-transcribed
iPSC DNA gene manipulation DNA
Zhou
fibroblast piPSC in vitro in vivo
pluripotency poly-arginine protein CPP(cell
transduction domain transcription factors C-terminus CPP penetrating peptides)
cell lysine arginine
amino acids
cell
paper
gene transcribe
translated
1962
JB Gurdon
!"#$%&'()*
+,-.(X.laevis)/0
12345
1998
JA Thomson
2003 MN„…e†|vz~x}‡z~
1998 JA Thomson ESC JB Gurdon et al. ˆ‰[
67&89:;<=>
$%1?@AXenopus
BCDoct-40E8(F
2007 Thomson Yamanaka GHIJ$KL
ES
2006
Yamakana et al.
Yamanaka 2009 review HIA]^123_`
a&bcde(fdgh
iPS teratoma ijk0lmnop/ 2007
UqrsYZ[ Yamakana et al.
Cell Stem Cell
`YZ[—˜(F”)*
Zhou et al., piPSC c…0šY›‚x›|vz~•œ
2007
iPSC Yamakana et al. Š‹ŒG•aŽ•*…e$
2009 %•Yw‘’}{(“G”•–
t*uvwxy/z{|{}~Yxw•
Yamakana et al. €v•{‚/UqƒsYZ[
2007
•{žY{Ÿ ¡¢YZ[0£¤ JA Thomson
¢¥¦§•r¨©ªa
XYZ[«I¬-
2009 `YZ[—˜(r™67
*…•/
Zhou et al.
*MNO@PQR0S
T/UVWXYZ[
3

4. 2007 Yamakana iPSC
1. low reprogramming efficiency OSKM factors pluripotent cell
2006 paper 0.01–0.5% 2007
Yamakana
2006 Fbx15 1/10 0.001–0.03%
factors
Oct4, Sox2, Klf4, and
2. genomic alterations due to viral integration
reverse transcribe OSKM DNA DNA c-Myc
3. c-Myc Klf-4 oncogene
telomere iPSC/piPSC
telomerase (~50 cycles)
ES cell telomerase telomere
2007 Yamanaka Nanog selection marker
iPSC hTERT(human
Telomerase Reverse Transcriptase) hES(human ES)cell
line hES iPSC
60
clone cell
doubling time
• 46.9 ± 12.4 (201B2)
• 47.8 ± 6.6 (201B6)
• 43.2 ± 11.5 (201B7)
•
hES doubling time clones
iPSC
telomere
GFP(Green Fluorescent Protein)
Chimera GFP transfection
Yamanaka paper GFP ”
” GFP Lasker
Nobel Prize
4

5. 2007 stem cell
gene targeting in mice
Bibliography
1. Campbell NA, Reece JB. BIOLOGY. 6th ed. Benjamin
iPSC piPSC
Cummings; 2001.
oncogene Literature
letter PNAS 1. , , , (2008) pp
”Distinguishing Cancerous iPSCs from ESCs” 20-26
iPSC ESC 2. Zhou et al., Generation of Induced Pluripotent Stem Cells
iPSC Using Recombinant Proteins, Cell Stem Cell (2009) pp.
1-4
3. JB Gurdon, The Developmental Capacity of Nuclei taken
from Intestinal Epithelium Cells of Feeding Tadpoles, J.
Cancerous iPSC Embryo. exp. Morph., (1962) pp. 622-40
4. JB Gurdon et al., Nuclei of Adult Mammalian Somatic
Cells Are Directly Reprogrammed to oct-4 Stem Cell
Gene Expression by Amphibian Oocytes, Current
Biology (2003) pp. 1206–1213
5. S Yamanaka et al., Induction of Pluripotent Stem Cells
from Mouse Embryonic and Adult Fibroblast Cultures by
Defined Factors, Cell, (2006) pp. 663-676
6. S Yamanaka et al., Generation of germline-competent
induced pluripotent stem cells, Nature, (2007) pp.
... 313-317
20 60~80 7. JA Thomson, Embryonic Stem Cell Lines Derived from
Human Blastocysts, Science, (1980) pp. 1145-47
8. S Yamanaka et al., Embryonic Stem Cell Lines Derived
from Human Blastocysts, Nature Biotechnology, (2009)
pp. 1-3
9. S Yamanaka et al., Induction of Pluripotent Stem Cells
from Adult Human Fibroblasts by Defined Factors, Cell,
(2007) pp. 861-872
10. JA Thomson et al., Induced Pluripotent Stem Cell Lines
Derived from Human Somatic Cells, Science Express,
(2007) pp. 1-4
11. RM Marion et al., Telomeres Acquire Embryonic Stem
Cell Characteristics in Induced Pluripotent Stem Cells,
Cell Stem Cell, (2009) pp. 141-154
or
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