Publicação: RG108 increases NANOG and OCT4 in bone marrow-derived mesenchymal cells through global changes in DNA modifications and epigenetic activation
dc.contributor.author | Assis, Rahyza I. F. | |
dc.contributor.author | Wiench, Malgorzata | |
dc.contributor.author | Silverio, Karina G. | |
dc.contributor.author | Silva, Rodrigo A. da [UNESP] | |
dc.contributor.author | Feltran, Georgia da Silva [UNESP] | |
dc.contributor.author | Sallum, Enilson A. | |
dc.contributor.author | Casati, Marcio Z. | |
dc.contributor.author | Nociti, Francisco H. | |
dc.contributor.author | Andia, Denise C. | |
dc.contributor.institution | Universidade Estadual de Campinas (UNICAMP) | |
dc.contributor.institution | Univ Birmingham | |
dc.contributor.institution | Universidade Estadual Paulista (Unesp) | |
dc.contributor.institution | Univ Paulista | |
dc.date.accessioned | 2019-10-04T12:33:03Z | |
dc.date.available | 2019-10-04T12:33:03Z | |
dc.date.issued | 2018-12-03 | |
dc.description.abstract | Human bone marrow-derived mesenchymal stem cells (hBMSCs) are important for tissue regeneration but their epigenetic regulation is not well understood. Here we investigate the ability of a non-nucleoside DNA methylation inhibitor, RG108 to induce epigenetic changes at both global and gene-specific levels in order to enhance mesenchymal cell markers, in hBMSCs. hBMSCs were treated with complete culture medium, 50 mu M RG108 and DMSO for three days and subjected to viability and apoptosis assays, global and gene-specific methylation/hydroxymethylation, transcript levels' analysis of epigenetic machinery enzymes and multipotency markers, protein activities of DNMTs and TETs, immunofluorescence staining and western blot analysis for NANOG and OCT4 and flow cytometry for CD105. The RG108, when used at 50 mu M, did not affect the viability, apoptosis and proliferation rates of hBMSCs or hydroxymethylation global levels while leading to 75% decrease in DNMTs activity and 42% loss of global DNA methylation levels. In addition, DNMT1 was significantly downregulated while TET1 was upregulated, potentially contributing to the substantial loss of methylation observed. Most importantly, the mesenchymal cell markers CD105, NANOG and OCT4 were upregulated being NANOG and OCT4 epigenetically modulated by RG108, at their gene promoters. We propose that RG108 could be used for epigenetic modulation, promoting epigenetic activation of NANOG and OCT4, without affecting the viability of hBMSCs. DMSO can be considered a modulator of epigenetic machinery enzymes, although with milder effect compared to RG108. | en |
dc.description.affiliation | Univ Estadual Campinas, Piracicaba Dent Sch, Dept Prosthodont & Periodont, Piracicaba, SP, Brazil | |
dc.description.affiliation | Univ Birmingham, Sch Canc Sci, Sch Dent, Birmingham, W Midlands, England | |
dc.description.affiliation | Sao Paulo State Univ, Biosci Inst, Dept Chem & Biochem, Botucatu, SP, Brazil | |
dc.description.affiliation | Univ Paulista, Sch Dent, Div Epigenet, Hlth Sci Inst, Sao Paulo, Brazil | |
dc.description.affiliationUnesp | Sao Paulo State Univ, Biosci Inst, Dept Chem & Biochem, Botucatu, SP, Brazil | |
dc.description.sponsorship | Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) | |
dc.description.sponsorship | FP7 Framework Marie Curie Actions Career Integration Grant (methDRE) | |
dc.description.sponsorshipId | FAPESP: 2013/09650-8 | |
dc.description.sponsorshipId | FAPESP: 2015/02160-0 | |
dc.format.extent | 20 | |
dc.identifier | http://dx.doi.org/10.1371/journal.pone.0207873 | |
dc.identifier.citation | Plos One. San Francisco: Public Library Science, v. 13, n. 12, 20 p., 2018. | |
dc.identifier.doi | 10.1371/journal.pone.0207873 | |
dc.identifier.issn | 1932-6203 | |
dc.identifier.uri | http://hdl.handle.net/11449/185146 | |
dc.identifier.wos | WOS:000451886500013 | |
dc.language.iso | eng | |
dc.publisher | Public Library Science | |
dc.relation.ispartof | Plos One | |
dc.rights.accessRights | Acesso aberto | |
dc.source | Web of Science | |
dc.title | RG108 increases NANOG and OCT4 in bone marrow-derived mesenchymal cells through global changes in DNA modifications and epigenetic activation | en |
dc.type | Artigo | |
dcterms.rightsHolder | Public Library Science | |
dspace.entity.type | Publication | |
unesp.campus | Universidade Estadual Paulista (Unesp), Instituto de Biociências, Botucatu | pt |
unesp.department | Química e Bioquímica - IBB | pt |