O******e
发帖数: 4845 | 1 Press Release
2012-10-08
The Nobel Assembly at Karolinska Institutet has today decided to award
The Nobel Prize in Physiology or Medicine 2012
jointly to
John B. Gurdon and Shinya Yamanaka
for the discovery that mature cells can be reprogrammed
to become pluripotent
Summary
The Nobel Prize recognizes two scientists who discovered that mature, specia
lised cells can be reprogrammed to become immature cells capable of developi
ng into all tissues of the body. Their findings have revolutionised our unde
rstanding of how cells and organisms develop.
John B. Gurdon discovered in 1962 that the specialisation of cells is revers
ible. In a classic experiment, he replaced the immature cell nucleus in an e
gg cell of a frog with the nucleus from a mature intestinal cell. This modif
ied egg cell developed into a normal tadpole. The DNA of the mature cell sti
ll had all the information needed to develop all cells in the frog.
Shinya Yamanaka discovered more than 40 years later, in 2006, how intact mat
ure cells in mice could be reprogrammed to become immature stem cells. Surpr
isingly, by introducing only a few genes, he could reprogram mature cells to
become pluripotent stem cells, i.e. immature cells that are able to develop
into all types of cells in the body.
These groundbreaking discoveries have completely changed our view of the dev
elopment and cellular specialisation. We now understand that the mature cell
does not have to be confined forever to its specialised state. Textbooks ha
ve been rewritten and new research fields have been established. By reprogra
mming human cells, scientists have created new opportunities to study diseas
es and develop methods for diagnosis and therapy.
Life a journey towards increasing specialisation
All of us developed from fertilized egg cells. During the first days after c
onception, the embryo consists of immature cells, each of which is capable o
f developing into all the cell types that form the adult organism. Such cell
s are called pluripotent stem cells. With further development of the embryo,
these cells give rise to nerve cells, muscle cells, liver cells and all oth
er cell types - each of them specialised to carry out a specific task in the
adult body. This journey from immature to specialised cell was previously c
onsidered to be unidirectional. It was thought that the cell changes in such
a way during maturation that it would no longer be possible for it to retur
n to an immature, pluripotent stage.
Frogs jump backwards in development
John B. Gurdon challenged the dogma that the specialised cell is irreversibl
y committed to its fate. He hypothesised that its genome might still contain
all the information needed to drive its development into all the different
cell types of an organism. In 1962, he tested this hypothesis by replacing t
he cell nucleus of a frog's egg cell with a nucleus from a mature, specialis
ed cell derived from the intestine of a tadpole. The egg developed into a fu
lly functional, cloned tadpole and subsequent repeats of the experiment yiel
ded adult frogs. The nucleus of the mature cell had not lost its capacity to
drive development to a fully functional organism.
Gurdon's landmark discovery was initially met with scepticism but became acc
epted when it had been confirmed by other scientists. It initiated intense r
esearch and the technique was further developed, leading eventually to the c
loning of mammals. Gurdon's research taught us that the nucleus of a mature,
specialized cell can be returned to an immature, pluripotent state. But his
experiment involved the removal of cell nuclei with pipettes followed by th
eir introduction into other cells. Would it ever be possible to turn an inta
ct cell back into a pluripotent stem cell?
A roundtrip journey mature cells return to a stem cell state
Shinya Yamanaka was able to answer this question in a scientific breakthroug
h more than 40 years after Gurdon磗 discovery. His research concerned embryo
nal stem cells, i.e. pluripotent stem cells that are isolated from the embry
o and cultured in the laboratory. Such stem cells were initially isolated fr
om mice by Martin Evans (Nobel Prize 2007) and Yamanaka tried to find the ge
nes that kept them immature. When several of these genes had been identified
, he tested whether any of them could reprogram mature cells to become pluri
potent stem cells.
Yamanaka and his co-workers introduced these genes, in different combination
s, into mature cells from connective tissue, fibroblasts, and examined the r
esults under the microscope. They finally found a combination that worked, a
nd the recipe was surprisingly simple. By introducing four genes together, t
hey could reprogram their fibroblasts into immature stem cells!
The resulting induced pluripotent stem cells (iPS cells) could develop into
mature cell types such as fibroblasts, nerve cells and gut cells. The discov
ery that intact, mature cells could be reprogrammed into pluripotent stem ce
lls was published in 2006 and was immediately considered a major breakthroug
h.
From surprising discovery to medical use
The discoveries of Gurdon and Yamanaka have shown that specialised cells can
turn back the developmental clock under certain circumstances. Although the
ir genome undergoes modifications during development, these modifications ar
e not irreversible. We have obtained a new view of the development of cells
and organisms.
Research during recent years has shown that iPS cells can give rise to all t
he different cell types of the body. These discoveries have also provided ne
w tools for scientists around the world and led to remarkable progress in ma
ny areas of medicine. iPS cells can also be prepared from human cells.
For instance, skin cells can be obtained from patients with various diseases
, reprogrammed, and examined in the laboratory to determine how they differ
from cells of healthy individuals. Such cells constitute invaluable tools fo
r understanding disease mechanisms and so provide new opportunities to devel
op medical therapies.
Sir John B. Gurdon was born in 1933 in Dippenhall, UK. He received his Docto
rate from the University of Oxford in 1960 and was a postdoctoral fellow at
California Institute of Technology. He joined Cambridge University, UK, in 1
972 and has served as Professor of Cell Biology and Master of Magdalene Coll
ege. Gurdon is currently at the Gurdon Institute in Cambridge.
Shinya Yamanaka was born in Osaka, Japan in 1962. He obtained his MD in 1987
at Kobe University and trained as an orthopaedic surgeon before switching t
o basic research. Yamanaka received his PhD at Osaka City University in 1993
, after which he worked at the Gladstone Institute in San Francisco and Nara
Institute of Science and Technology in Japan. Yamanaka is currently Profess
or at Kyoto University and also affiliated with the Gladstone Institute.
Key publications:
Gurdon, J.B. (1962). The developmental capacity of nuclei taken from intesti
nal epithelium cells of feeding tadpoles. Journal of Embryology and Experime
ntal Morphology 10:622-640.
Takahashi, K., Yamanaka, S. (2006). Induction of pluripotent stem cells from
mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:
663-676. |
|
