Induced Pluripotent Stem Cells in Medicine and Biology
Induced Pluripotent Stem Cells in Medicine and Biology
Induced Pluripotent Stem Cells in Medicine and Biology
Introduction
All cells that exist in the body, both somatic (of all three germ layers)
and germ cells, originate from the pluripotent cells of the embryo.
The recently developed induced pluripotent stem cell (iPSC)
technology, which enables the induction of pluripotency in mature
somatic cells by treatment with defined factors, has created new
avenues in basic research, disease modeling and regenerative
medicine (Takahashi and Yamanaka, 2006). However, as the
proverbial phrase goes, Rome wasnt built in a day and in fact the
foundations of this field go back over 50 years. In groundbreaking
work, Sir John Gurdon succeeded in generating cloned frogs by
transferring the nucleus of a tadpoles somatic cell into an oocyte
(Gurdon, 1962) (Fig. 1A). His remarkable study demonstrated that
the oocyte can completely reverse the acquired memories of somatic
cells. Before his breakthrough, differentiation had long been
considered to be a one-way street, with traffic flowing from an
immature state, a stem or progenitor cell, to a more mature
differentiated state. This is often depicted by the epigenetic
landscape proposed by Conrad Waddington (Waddington, 1957)
(Fig. 2). In parallel, it was previously believed that unnecessary
genetic information was deleted or terminally inactivated in cells
committed to a specific state, a theory known as Weismanns barrier
(Weismann, 1893). Nuclear reprogramming demonstrated that not
only do somatic cells retain all genetic information, but they can
also be rejuvenated by artificial manipulations to again acquire
pluripotency.
Another key discovery in scientific history that enabled us to
generate iPSCs was a landmark experiment that first demonstrated
direct cell fate conversion by a defined transcription factor (Davis et
al., 1987) (Fig. 1B). The authors of that study performed
complementary DNA subtraction and found three genes that were
expressed predominantly in proliferative myoblasts. Enforced
expression of one of them, myogenic differentiation 1 (Myod1), was
1
Center for iPS Cell Research and Application, Kyoto University, Kyoto, 606-8507,
Japan. 2Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94158,
USA.
*Authors for correspondence ([email protected];
[email protected])
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Summary
2458 SPOTLIGHT
Pluripotency
Nuclear transfer
+
B
TF
Differentiation
(Normal development)
Reprogramming
(Induction of pluripotency)
Lineage conversion
(Trans-differentiation)
Lineage conversion
(Trans-differentiation)
TF TF
Induced pluripotency
TF
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SPOTLIGHT 2459
DEVELOPMENT
Funding
This work was supported in part by a grant from the Program for Promotion of
Fundamental Studies in Health Sciences of National Institute of Biomedical
Innovation, a grant from the Leading Project of Ministry of Education, Culture,
Sports, Science and Technology (MEXT), a grant from the Funding Program for
World-Leading Innovative Research and Development on Science and
Technology (FIRST) of the Japan Society for the Promotion of Science, Grantsin-Aid for Scientific Research of the Japan Society for the Promotion of Science
and MEXT.
Competing interests statement
S.Y. is a member without salary of the scientific advisory boards of iPierian, iPS
Academia Japan, Megakaryon Corporation and Retina Institute Japan.
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