Variable Reprogramming of the Pluripotent Stem Cell Marker Oct4 in Mouse Clones: Distinct Developmental Potentials in Different Culture Environments.

A prevailing view of cloning by somatic-cell nuclear transfer
is that reprogramming of gene expression occurs during the
first few hours after injection of the nucleus into an oocyte,
that the process is stochastic, and that the type of reprogramming
needed for cloning success is foreign and unlikely to be
readily achieved in the ooplasm. Here, we present evidence
that the release of reprogramming capacity is contingent on
the culture environment of the clone while the contribution of
aneuploidy to altered gene expression is marginal. In particular,
the rate of blastocyst formation in clones and the regional
distribution of mRNA for the pluripotent stem cell marker
Oct4 in clonal blastocysts was highly dependent on the culture
environment after cumulus cell nuclear transfer, unlike that
in genetically equivalent zygotes. Epigenetic modifications of
genetically identical somatic nuclei continue after the first cell
division of the clones and are amenable to a degree of experimental
control, and their development to the blastocyst stage
and appropriate expression of Oct4 predict further outcome,
such as derivation of embryonic stem (ES) cells, but not fetal
development. This observation indicates that development to
the blastocyst stage is not equivalent to full reprogramming
and lends support to the novel concept that ES cells are not
the equivalent of the inner cell mass, hence the discrepancy
between ES cell derivability and fetal development of clones.