Appendix H. 
Human Embryonic Germ Cells: 
June 2001 - July 2003 
The Published Record 
JOHN GEARHART, PH.D. 
C. Michael Armstrong Professor, Institute for Cell Engineering, 
Johns Hopkins University School of Medicine 
There have been but tv\ro original research articles published on 
human embryonic germ cell in the period covered by this report. It is 
appropriate that only peer-reviewed articles be considered in this 
report, as the field of stem cell research is rife with undocumented or 
unsubstantiated claims. There have been several pubhcations on EG 
cells derived in mice and chick and comment will be made on these 
reports as they may impact on the eventual use or study of the 
human cells. 
There is a concern, given the imprinting-based developmental 
abnormalities observed in humans, and those that have been 
produced experimentally in animals, that dysregulated gene 
expression in stem cell derived tissues could pose a serious problem 
in the use of such tissues for cell-based therapies. Genomic 
imprinting is defined as an epigenetic modification of the DNA (other 
than sequence) in the germ line that leads to the preferential 
expression of a specific allele (monoallelic expression) of some genes 
in the somatic cells of the offspring in a parental dependent manner. 
Because a maternal gene allele may be a paternal allele in the next 
generation, the imprinting must be reprogrammed in the germ line, 
that is, the epigenetic ‘marks’ must be erased (during germ cell 
development) and established in the newly formed embryo. The 
timing of the erasure in humans is not known. Imprinting involves 
methylation at specific sites in the DNA and most likely, other 
changes as well. 
There have been several reports from experiments with the mouse 
that indicate that imprinting is abnormal in pluripotent stem cells 
derived from mouse embryos. These studies include abnormal or 
variable imprints in mouse EG cells, abnormal imprints in ES cells 
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