THE 2012 Nobel Prize in Physiology or Medicine has been awarded to
twoscientists for discoveries that have led to a paradigm shift in our
understanding of how immature cells differentiate and
becomespecialised cells in the body of an organism— such as neurons,
muscle and skin cells—and the plasticity of the differentiated state.
JohnB. Gurdon, 79, of the Gurdon Institute, Cambridge, United Kingdom,
and Shinya Yamanaka, 50, of Kyoto University, Japan, and Gladstone
Institutes, San Francisco, California, United States, showed in
different experiments that "mature, differentiated cells can be
reprogrammed to become pluripotent".
Gurdon discovered in 1962 that the specialisation of cells is
reversible. Yamanaka, who was born coincidentally in the same year as
Gurdon's discovery, showed in 2006 how intact mature cells in mice
could be reprogrammed by clever introduction of some genes to become
immature stem cells. Their findings have revolutionised our
understanding of how cells and organisms develop. We now know that
differentiation is nota unidirectional process, as was believed
earlier, and that mature cells need not remain locked forever in their
specialised states. Gurdonand Yamanaka showed that, under some
conditions, the clock of cellular development can be turned back.
During normal development, the egg cells and cells in the early embryo
proceed from theinitial undifferentiated state into a more specialised
state by differentiation. In an adult organism, different kinds of
differentiated cell types are needed to perform different specialised
tasks. The fertilised egg and the cells of the embryo in theearliest
stage of its development (the zygote) can give rise to all types of
cells in the embryo, as well as extra-embryonic tissues such asthe
placenta, and hence they are termed totipotent. During the development
process, cells at the blastocyst stage begin to be distinguished. The
cells inthe inner cell mass—the embryonic stem (ES) cells—are
pluripotent. That is, they can give rise to all somatic cells as
wellas to cells that become gametes (eggs and sperm).
Cells progressively become restricted in their differentiation
potential and thus do notretain their pluripotency.This maturation of
cells results in most cells becoming fully differentiated. The process
also results in theformation of cells with limited and specialised
potency—the somatic or adult stem cells. They remain in certain
locations in the body such as bone marrow, intestine, and skin and act
as the reservoir for cell maintenance and repair machinery.
Differentiated cells are very stable and do not, asa rule, become
cells of any other type or revert to the early undifferentiated state.
The long-standing dogma in biology, therefore, was that somatic or
adult cells were permanently lockedin the specialised state ofa
specific part of the body and that the journey back to the
undifferentiated, embryo-like, stem cell state was impossible.
Thespecific pattern of expression of functional proteins in
differentiatedcells also suggested that these carried irreversible
genetic modifications that rendered induction of pluripotency in them
impossible.
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