{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Gomes Fernandes M"],"funding":["Netherlands organization of Scientific Research","Fundação para a Ciência e Tecnologia","Interuniversity Attraction Poles","Dutch Research Council (NWO)","Scientific Research-Flanders","Bontius Stichting"],"pagination":["85-94"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4720007"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["6(1)"],"pubmed_abstract":["Naive mouse embryonic stem cells (mESCs) are in a metastable state and fluctuate between inner cell mass- and epiblast-like phenotypes. Here, we show transient activation of the BMP-SMAD signaling pathway in mESCs containing a BMP-SMAD responsive reporter transgene. Activation of the BMP-SMAD reporter transgene in naive mESCs correlated with lower levels of genomic DNA methylation, high expression of 5-methylcytosine hydroxylases Tet1/2 and low levels of DNA methyltransferases Dnmt3a/b. Moreover, naive mESCs, in which the BMP-SMAD reporter transgene was activated, showed higher resistance to differentiation. Using double Smad1;Smad5 knockout mESCs, we showed that BMP-SMAD signaling is dispensable for self-renewal in both naive and ground state. These mutant mESCs were still pluripotent, but they exhibited higher levels of DNA methylation than their wild-type counterparts and had a higher propensity to differentiate. We showed that BMP-SMAD signaling modulates lineage priming in mESCs, by transiently regulating the enzymatic machinery responsible for DNA methylation."],"journal":["Stem cell reports"],"pubmed_title":["BMP-SMAD Signaling Regulates Lineage Priming, but Is Dispensable for Self-Renewal in Mouse Embryonic Stem Cells."],"pmcid":["PMC4720007"],"funding_grant_id":["ASPASIA 015.007.037","015.007.037","SFRH/BD/94387/2013","SFRH/BD/78689/2011","IUAP/PAI P7/14"],"pubmed_authors":["Van Criekinge W","Maas E","Umans L","Huylebroeck D","Szuhai K","Mummery C","Deforce D","Zwijsen A","Gomes Fernandes M","Roost MS","Semrau S","Abon Escalona V","Ramakrishnan R","Dries R","Salvatori D","de Sousa Lopes SM","de Melo Bernardo A","Davis RP"],"additional_accession":[]},"is_claimable":false,"name":"BMP-SMAD Signaling Regulates Lineage Priming, but Is Dispensable for Self-Renewal in Mouse Embryonic Stem Cells.","description":"Naive mouse embryonic stem cells (mESCs) are in a metastable state and fluctuate between inner cell mass- and epiblast-like phenotypes. Here, we show transient activation of the BMP-SMAD signaling pathway in mESCs containing a BMP-SMAD responsive reporter transgene. Activation of the BMP-SMAD reporter transgene in naive mESCs correlated with lower levels of genomic DNA methylation, high expression of 5-methylcytosine hydroxylases Tet1/2 and low levels of DNA methyltransferases Dnmt3a/b. Moreover, naive mESCs, in which the BMP-SMAD reporter transgene was activated, showed higher resistance to differentiation. Using double Smad1;Smad5 knockout mESCs, we showed that BMP-SMAD signaling is dispensable for self-renewal in both naive and ground state. These mutant mESCs were still pluripotent, but they exhibited higher levels of DNA methylation than their wild-type counterparts and had a higher propensity to differentiate. We showed that BMP-SMAD signaling modulates lineage priming in mESCs, by transiently regulating the enzymatic machinery responsible for DNA methylation.","dates":{"release":"2016-01-01T00:00:00Z","publication":"2016 Jan","modification":"2026-05-05T11:59:18.415Z","creation":"2026-04-07T21:42:32.619Z"},"accession":"S-EPMC4720007","cross_references":{"pubmed":["26711875"],"doi":["10.1016/j.stemcr.2015.11.012"]}}