| Summary: | Epigenetic mechanisms such as DNA methylation and histone modification are
important in stem cell differentiation. Methylation is principally associated
with transcriptional repression, and histone acetylation is correlated with an
active chromatin state. We determined the effects of these epigenetic mechanisms
on adipocyte differentiation in mesenchymal stem cells (MSCs) derived from bone
marrow (BM-MSCs) and adipose tissue (ADSCs) using the chromatin-modifying agents
trichostatin A (TSA), a histone deacetylase inhibitor, and
5-aza-2′-deoxycytidine (5azadC), a demethylating agent. Subconfluent MSC
cultures were treated with 5, 50, or 500 nM TSA or with 1, 10, or
100 µM 5azadC for 2 days before the initiation of adipogenesis. The
differentiation was quantified and expression of the adipocyte genes PPARG and
FABP4 and of the anti-adipocyte gene GATA2 was evaluated. TSA decreased
adipogenesis, except in BM-MSCs treated with 5 nM TSA. Only treatment
with 500 nM TSA decreased cell proliferation. 5azadC treatment decreased
proliferation and adipocyte differentiation in all conditions evaluated,
resulting in the downregulation of PPARG and FABP4 and the upregulation of
GATA2. The response to treatment was stronger in ADSCs than in BM-MSCs,
suggesting that epigenetic memories may differ between cells of different
origins. As epigenetic signatures affect differentiation, it should be possible
to direct the use of MSCs in cell therapies to improve process efficiency by
considering the various sources available.
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