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2015 ; 4
(6
): 955-60
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Human Germline: A New Research Frontier
#MMPMID26028529
Surani MA
Stem Cell Reports
2015[Jun]; 4
(6
): 955-60
PMID26028529
show ga
We recently elucidated the mechanism of human primordial germ cell (hPGC)
specification and resetting of the epigenome for totipotency. The regulators of
hPGC specification also initiate resetting of the epigenome, leading to a
comprehensive erasure of DNA methylation, erasure of imprints and X reactivation
in early hPGCs in vivo. These studies reveal differences with the mouse model,
which are probably due to differences in the regulation of human pluripotency,
and in postimplantation development at gastrulation, which indicates the
importance of non-rodent models for investigations. Within the extreme
hypomethylated environment of the early human germline are loci that are
resistant to DNA demethylation, with subsequent predominant expression in neural
cells. These loci provide a model for studies on the mechanism of
transgenerational epigenetic inheritance, and their response to environmental
factors. Such epigenetic mechanism of inheritance could potentially provide
greater phenotypic plasticity, with significant consequences for human
development and disease.