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Monitoring Stem Cell Research 
stem cell. Erasure of the epigenetic memory has major consequences 
for the "normalcy" of embryonic stem cells. 
(ii) The derivation of embryonic stem cells is a highly selective process 
that erases the “epigenetic memory" of the donor nucleus 
Embryonic stem cells, regardless of whether they have been 
generated from a fertilized egg or by SCNT, are derived from the cells 
of a blastocyst that have been explanted and propagated in tissue 
culture. Of the blastocyst cells that are explanted in this way, those 
that derive from the portion of the blastocyst termed the inner cell 
mass (ICM) initially express “key" embryonic genes such as Oct-4. 
However, soon after explantation, most ICM cells extinguish Oct-4 
expression and cease proliferating (Buehr et al., 2003). Only one or a 
few of the ICM-derived cells will eventually re-express Oct-4 and 
these few Oct-4-positive cells are those that resume rapid 
proliferation, yielding the cell populations that we designate as 
"embryonic stem" cells. These cells represent a cell population that 
has no equivalent in the normal embryo and may be considered a 
tissue culture artifact, though a useful one (Fig. 6). 
The important point for this discussion is that the propagation of 
blastocyst cells in vitro results in a rare population of surviving cells 
that have erased the “epigenetic memory" of the donor nucleus. This 
process results ultimately in ES cells that have, regardless of donor 
nuclear origin, an identical developmental potential. In other words, 
ES cells derived from embryos produced by normal fertilization and 
those produced from cloned embryos are functionally 
indistinguishable (Hochedlinger and Jaenisch, 2002b; Rideout et al., 
2002; Wakayama et al., 2001). Because the ES cells that derive from 
normally fertilized embryos are able to participate in the generation 
of all normal embryonic tissues, we can conclude that the ES cells 
derived from cloned embryos have a similar potential to generate the 
full range of normal tissues. 
(Hi) ES cells, epigenetic instability and therapeutic potential 
Epigenetic instability appears to be a consistent characteristic of ES 
cells. This was shown when individual ES cells were analyzed for 
expression of imprinted genes: even cells in a recently subcloned ES 
cell line differed strongly in the expression of genes such as HI 9 or 
Igf2. The variable expression was correlated with the DNA 
methylation status of the genes, which switched from an 
unmethylated to a methylated state between sister cells (Humpherys 
et al., 2001). This was a surprising result in view of the known 
potential of ES cells to generate terminally differentiated cells that 
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