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DNMT3B controls fates in human pluripotent and
nullipotent stem cells
Patompon Wongtrakoongate and Peter W. Andrews
Centre for Stem Cell Biology, Sheffield, United Kingdom
DNMT3B is a de novo DNA methyltransferase highly expressed
in embryonic stem (ES) and embryonal carcinoma (EC) cells.
To determine DNMT3B function in human ES and EC cells, we
have established inducible DNMT3B knockdown of human ES
cells, and of both human pluripotent and nullipotent EC cells. We
find that DNMT3B does not inhibit differentiation and apoptosis in
pluripotent ES and EC cells. On the other hand, it facilitates differentiation of human ES cells, and acts as a barrier of induced
pluripotency, suggesting its role in closed chromatin state. In
contrast to the pluripotent stem cells, DNMT3B is required to
prevent apoptosis in the nullipotent EC cells. In addition, Aza-dC
treatment induced both differentiation and apoptotic fates of the
pluripotent ES and EC cells, though only an apoptotic fate for
the nullipotent EC cells. Consistent with earlier studies, these
responses are mediated by the presence of DNMT3B, indicating
a strong interaction between DNMT3B and chromatin in the stem
cells. Similar to DNMT3B knockdown, silencing of OCT4 in nullipotent EC cells, which down-regulated DNMT3B expression,
resulted in cells undergoing apoptosis. Moreover, the OCT4
knockdown differentiated cells did not undergo apoptosis induced
by Aza-dC. We conclude that DNMT3B is crucial for human pluripotent and nullipotent stem cells to alter their fates, and provide
an evidence of the epigenetic drug that targets only cancer stem
cell component but not their differentiated counterpart.