ISSN 1022-7954, Russian Journal of Genetics, 2008, Vol. 44, No. 12, pp. 1377–1393. © Pleiades Publishing, Inc., 2008.
Original Russian Text © S.P. Medvedev, A.I. Shevchenko, N.A. Mazurok, S.M. Zakian, 2008, published in Genetika, 2008, Vol. 44, No. 12, pp. 1589–1608.
PHENOMENON OF PLURIPOTENCY
OF MAMMALIAN CELLS IN VIVO
AND IN VITRO
An adult mammalian organism consists of more
than 200 specialized cell types. The whole diversity of
cell types is formed in the course of embryo develop-
ment from a single zygote cell . In preimplantation
embryogenesis of mammals, the ﬁrst differentiation
event occurs during the fourth zygote division. The
resulting embryo, morula, is subdivided into large outer
and small inner cells. At the next stage of development
(blastocyst), the morula outer cells form the extraem-
bryonic epithelial layer (trophectoderm), which is
required for the implantation of the embryo in the
uterus. The inner part of the morula cells is transformed
in the inner cell mass (ICM) of the blastocyst. Before
implantation, the ICM is divided in two cell lines: epi-
blast (primitive/embryonic ectoderm), which then will
gives rise to three germinal layers and to primordial
germinal cells, and hypoblast (primitive/embryonic
endoderm), from which two extraembryonic lines
develop: visceral and parietal entoderms .
Lines of embryonic stem cells (ES cells) are derived
from embryos at the blastocyst stage. ES cells have
some speciﬁc features of ICM and epiblast cells.
Among them the main one is pluripotency. Pluripo-
tency is the ability of stem cells to give rise after differ-
entiation to derivatives of three germinal layers (ecto-
derm, endoderm, and mesoderm) and to functional
Pluripotency of ES cells is most completely mani-
fested when producing chimeric animals. ES cells
obtained from blastocysts can be again successfully
returned into the blastocyst. The embryos in this case
develop normally, and the injected ES cells can give
rise to cells of any tissue, including functional gametes.
If ES cells give rise to functional gametes, any genetic
manipulations (introduction of genetic constructions in
the genome, directional gene mutations) made with ES
cells in culture are transmitted to the next generation.
This property of ES cells offers considerable scope for
their use in producing transgenic animals .
One more fact in favor of a wide potential of ES
cells to differentiate into various cell types is that in the
case of injecting ES cells to immunodeﬁcient mice with
mutation, the formation of teratocarcinomas
consisting of derivatives of all three germinal layers
takes place .
ICM and ES cells are not equivalent. The pluripo-
tent state of ICM cells is temporary. They cannot be
considered as an in vivo existing compartment of stem
cells. Embryonic stem cells exist exclusively in vitro
and undergo certain selection and adaptation to the cul-
One more remarkable characteristic of ES cells is
their ability to preserve undifferentiated state through-
out long-term passaging under optimal conditions.
Embryonic stem cells are characterized by symmetric
division. Two identical pluripotent cells are formed
after division of each ES cell. At present, much atten-
tion is given to the molecular bases of establishment
and maintenance of the pluripotent state of cells.
Several genes and molecular signaling pathways
involved in the maintenance of the pluripotent state of
ICM and epiblast cells and pluripotency and self-
renewal of cells in culture have been identiﬁed 
Are the Key Genes in the System
of Pluripotency Maintenance in Mammalian Cells
S. P. Medvedev, A. I. Shevchenko, N. A. Mazurok, and S. M. Zakian
Institute of Cytology and Genetics, Russian Academy of Sciences,
Novosibirsk, 630090 Russia;
Received February 7, 2008
—Embryonic stem cells are able to give rise after differentiation to derivatives of three germinal layers
(ectoderm, endoderm, and mesoderm) and to functional gametes. This property of cells is referred to as pluri-
potency. The pluripotent status of preimplantation embryo cells and embryonic stem cells is maintained by a
complex system of molecular signaling pathways and transcription factors. The key regulators in this system
are the transcription factors OCT4 and NANOG. The role and place of these factors in the pluripotency-main-
taining system and their interaction with other factors are considered in the review. Data are presented on the
structure, chromosomal location, expression, and regulation of the
genes in mammals.
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