Publicação:
RG108 increases NANOG and OCT4 in bone marrow-derived mesenchymal cells through global changes in DNA modifications and epigenetic activation

dc.contributor.authorAssis, Rahyza I. F.
dc.contributor.authorWiench, Malgorzata
dc.contributor.authorSilverio, Karina G.
dc.contributor.authorSilva, Rodrigo A. da [UNESP]
dc.contributor.authorFeltran, Georgia da Silva [UNESP]
dc.contributor.authorSallum, Enilson A.
dc.contributor.authorCasati, Marcio Z.
dc.contributor.authorNociti, Francisco H.
dc.contributor.authorAndia, Denise C.
dc.contributor.institutionUniversidade Estadual de Campinas (UNICAMP)
dc.contributor.institutionUniv Birmingham
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionUniv Paulista
dc.date.accessioned2019-10-04T12:33:03Z
dc.date.available2019-10-04T12:33:03Z
dc.date.issued2018-12-03
dc.description.abstractHuman 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.affiliationUniv Estadual Campinas, Piracicaba Dent Sch, Dept Prosthodont & Periodont, Piracicaba, SP, Brazil
dc.description.affiliationUniv Birmingham, Sch Canc Sci, Sch Dent, Birmingham, W Midlands, England
dc.description.affiliationSao Paulo State Univ, Biosci Inst, Dept Chem & Biochem, Botucatu, SP, Brazil
dc.description.affiliationUniv Paulista, Sch Dent, Div Epigenet, Hlth Sci Inst, Sao Paulo, Brazil
dc.description.affiliationUnespSao Paulo State Univ, Biosci Inst, Dept Chem & Biochem, Botucatu, SP, Brazil
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipFP7 Framework Marie Curie Actions Career Integration Grant (methDRE)
dc.description.sponsorshipIdFAPESP: 2013/09650-8
dc.description.sponsorshipIdFAPESP: 2015/02160-0
dc.format.extent20
dc.identifierhttp://dx.doi.org/10.1371/journal.pone.0207873
dc.identifier.citationPlos One. San Francisco: Public Library Science, v. 13, n. 12, 20 p., 2018.
dc.identifier.doi10.1371/journal.pone.0207873
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/11449/185146
dc.identifier.wosWOS:000451886500013
dc.language.isoeng
dc.publisherPublic Library Science
dc.relation.ispartofPlos One
dc.rights.accessRightsAcesso aberto
dc.sourceWeb of Science
dc.titleRG108 increases NANOG and OCT4 in bone marrow-derived mesenchymal cells through global changes in DNA modifications and epigenetic activationen
dc.typeArtigo
dcterms.rightsHolderPublic Library Science
dspace.entity.typePublication
unesp.campusUniversidade Estadual Paulista (Unesp), Instituto de Biociências, Botucatupt
unesp.departmentQuímica e Bioquímica - IBBpt

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