Biomedical Engineering Reference
In-Depth Information
et al., 2004), whereas JmjC-domain-containing proteins remove methyl groups
through a hydroxylation reaction that requires alpha-ketoglutarate and Fe(II)
as cofactors (Tsukada et al., 2006). Jmjd2c has a different specificity and is
shown to convert H3K9 and H3K36 from trimethylation to dimethylation
(Whetstine et al., 2006). Loh et al demonstrated that Jmjd1 and Jmjd2c expres-
sion are under Oct4 regulation. Either Jmjd1a or Jmjd2c depletion induces
ESCs differentiation (Loh et al., 2007). This suggests that histone demethylases
may also play important role in the ESCs transcriptional network and may
specify the epigenetic status of pluripotency-associated genes.
7 State of ESCs
We have broadly reviewed the state of pluripotency from multiple perspectives:
extrinsic factors, transcription factors, protein complexes, and the genome-wide
chromatin state. In just a few years, investigators have generated extensive
resources to address the pluripotent state. It is evident that the pluripotent state
is not static, but highly dynamic. Pluripotency may depend on the extent to which
cells may be maintained in a ''poised state'', reflecting the balance between
proliferation and differentiation. A principal distinction between ESCs and
adult stem cells relates to their modes of cell division. Adult stem cells are believed
to divide asymmetrically in order to generate two cell types, one committed to
self-renewal and the other to differentiation. In contrast, ESCs divide symme-
trically to produce identical daughters. The progenitors arising from a symme-
trical division may subsequently choose to remain pluripotent or differentiate.
For example, Nanog is indispensable for early development, however, its expres-
sion is surprisingly dynamic among ESCs. Hence, ESCs appear metastable,
balancing between two states, self-renewal and pro-differentiation. Unlike adult
stem cells, which only need to supply a limited cell type, this metastable nature of
ESCs has an advantage in early embryogenesis, which necessitates generating
diverse cell types in a short period. Presently, many investigators seek to differ-
entiate ESCs to specific cell lineages. However, it is hard to define conditions to
differentiate ESCs toward an uniform cell type. This metastable nature of ESCs,
which may have an advantage in embryogenesis, complexes isolation of pure cell
type in vitro. The state of pluripotency is highly dynamic. Further mechanistic
understanding of pluripotency may facilitate use of ESCs as potential cellular
sources in regeneration medicine and independently stimulate comparisons of
pluripotency and the malignant phenotype.
References
Ananiev, G.E., Goldstein, S., Runnheim, R., Forrest, D.K., Zhou, S., Potamousis, K.,
Churas, C.P., Bergendahl, V., Thomson, J.A., Schwartz, D.C., 2008. Optical mapping
discerns genome wide DNA methylation profiles. BMC Mol Biol 9, 68.
