The epigenetic modifiers 5-aza-2'-deoxycytidine and trichostatin A influence adipocyte differentiation in human mesenchymal stem cells
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 epigeneti...
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Associação Brasileira de Divulgação
Científica
2013
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3854397/ |
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pubmed-38543972013-12-16 The epigenetic modifiers 5-aza-2'-deoxycytidine and trichostatin A influence adipocyte differentiation in human mesenchymal stem cells Zych, J. Stimamiglio, M.A. Senegaglia, A.C. Brofman, P.R.S. Dallagiovanna, B. Goldenberg, S. Correa, A. Biomedical Sciences 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. Associação Brasileira de Divulgação Científica 2013-05-28 /pmc/articles/PMC3854397/ /pubmed/23797495 http://dx.doi.org/10.1590/1414-431X20132893 Text en http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Zych, J. Stimamiglio, M.A. Senegaglia, A.C. Brofman, P.R.S. Dallagiovanna, B. Goldenberg, S. Correa, A. |
| spellingShingle |
Zych, J. Stimamiglio, M.A. Senegaglia, A.C. Brofman, P.R.S. Dallagiovanna, B. Goldenberg, S. Correa, A. The epigenetic modifiers 5-aza-2'-deoxycytidine and trichostatin A influence adipocyte differentiation in human mesenchymal stem cells |
| author_facet |
Zych, J. Stimamiglio, M.A. Senegaglia, A.C. Brofman, P.R.S. Dallagiovanna, B. Goldenberg, S. Correa, A. |
| author_sort |
Zych, J. |
| title |
The epigenetic modifiers 5-aza-2'-deoxycytidine
and trichostatin A influence adipocyte differentiation in human mesenchymal stem
cells |
| title_short |
The epigenetic modifiers 5-aza-2'-deoxycytidine
and trichostatin A influence adipocyte differentiation in human mesenchymal stem
cells |
| title_full |
The epigenetic modifiers 5-aza-2'-deoxycytidine
and trichostatin A influence adipocyte differentiation in human mesenchymal stem
cells |
| title_fullStr |
The epigenetic modifiers 5-aza-2'-deoxycytidine
and trichostatin A influence adipocyte differentiation in human mesenchymal stem
cells |
| title_full_unstemmed |
The epigenetic modifiers 5-aza-2'-deoxycytidine
and trichostatin A influence adipocyte differentiation in human mesenchymal stem
cells |
| title_sort |
epigenetic modifiers 5-aza-2'-deoxycytidine
and trichostatin a influence adipocyte differentiation in human mesenchymal stem
cells |
| description |
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. |
| publisher |
Associação Brasileira de Divulgação
Científica |
| publishDate |
2013 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3854397/ |
| _version_ |
1612035884422529024 |