Discovery helps answer how stem cells act
By Neil Neumann
Issue date: 2/14/08
PrintEmail Article Tools Page 1 of 2 next > In a recent journal
article, researchers from the Hopkins School of Medicine's Institute
of Cell Engineering (ICE) show that cellular markers of embryonic
germ cell (EGC) pluripotency are also expressed on primordial germ
cells (PGC) in the human fetal ovary.
Every cell in your body can be traced back to a single cell, the
fertilized egg. Early in development, every cell in the embryo can
theoretically develop into any one of the hundreds of cell types in a
mature body. Some of these "undifferentiated" cells live on even into
adulthood.
In stem cell biology, there are multiple levels of differentiation
upon which cell types in a certain state are allowed to mature to
other, more specific cells. Totipotent cells are those which can
produce any cell in the body, as well as placental cells.
Pluripotent cells can give rise to any cell in the body, including
germ cells, or sperm and egg cells. Multipotent and unipotent cells
are limited in their ability to differentiate (except in special
cases of transdifferentiatio
For example, an in vivo muscle stem cell is unable to produce a
neuron, and vice versa. With that said, manipulations in vitro can
allow regressions to a more immature state such as mouse embryonic
fibroblasts reverting to embryonic stem cells.
Developmentally, several days after fertilization of the female
oocyte by the male sperm, certain cell-types begin to emerge.
There are the pluripotent inner cell mass (ICM) cells that give rise
to the embryo that develops into bodily tissues and organs. From here
there is a clear separation of the somatic cell lineages compared to
the germ cells.
Germ cells are cells that give rise to the germline such as sperm and
oocytes. The PGCs arise from the ICM and eventually mature into sperm
or oocytes. From the PGCs, pluripotent EGCs can be derived.
All cells in the developing embryo are destined for the somatic cell
line, so it is paramount that the germ cells repress that fate. Upon
migration to the genital ridge, the PGCs go through extensive erasing
of the epigenetic modifications and allow the PGCs to regenerate a
totipotent cell.
The PGCs then form the germ cells, which upon maturation, can be used
to reproduce.
Since embryonic germ cells are pluripotent stem cells derived from
fetal tissue (PGCs), it would follow that these cells express highly
similar, but distinct, cell markers.
Before this paper, from the laboratory of world-renowned stem cell
researcher John D. Gearhart, no one had looked at the gene expression
levels of certain key pluripotency genes. This is what his team set
out to find.
The results show that within 5.5 to 15 weeks post-fertilization,
there were distinct populations of PGCs that expressed pluripotency
markers such as cKIT, Nanog, OCT4 and VASA. Furthermore, these cells
expressed SSEA1, SSEA4 and had alkaline phosphatase activity, all of
which are evidence for pluripotency.
The researchers also wanted to show the ability of these PGC
populations to give rise to pluripotent EGCs. The EGCs were derived
from SSEA1+ PGCs and Gearhart et al. show that a positive correlation
exists between the number of OCT4+ cells and efficiency of derivation.
The expression of cell markers TRA-1-60 and TRA-1-81 were limited to
the EGCs, showing a distinct but highly similar expression profile
for the unipotent PGCs and the pluripotent EGCs.
These results demonstrate an enhanced understanding of developmental
biology and the importance of pluripotency genes in germ cell fate.
According to Gearhart, researchers need to understand these results
and see that they should not only be looking at expression of a set
of genes, but should instead focus on seeing the diversity within a
population of cells and how that influences pluripotency.
Future studies will look at how cells become pluripotent and which
pathways are involved in this transformation.
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StemCells subscribers may also be interested in these sites:
Children's Neurobiological Solutions
http://www.CNSfoundation.org/
Cord Blood Registry
http://www.CordBlood.com/at.cgi?a=150123
The CNS Healing Group
http://groups.yahoo.com/group/CNS_Healing
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