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BMP-SMAD signaling regulates lineage priming, but is dispensable for self-renewal in mouse embryonic stem cells

(2016) STEM CELL REPORTS. 6(1). p.85-94
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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.
Keywords
EQUILIBRIUM, DEMETHYLATION, DIFFERENTIATION, HETEROGENEITY, GENE-EXPRESSION, TRANSCRIPTIONAL NETWORK, GROUND-STATE PLURIPOTENCY

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MLA
Gomes Fernandes, Maria, Ruben Dries, Matthias S Roost, et al. “BMP-SMAD Signaling Regulates Lineage Priming, but Is Dispensable for Self-renewal in Mouse Embryonic Stem Cells.” STEM CELL REPORTS 6.1 (2016): 85–94. Print.
APA
Gomes Fernandes, M., Dries, R., Roost, M. S., Semrau, S., de Melo Bernardo, A., Davis, R. P., Ramakrishnan, R., et al. (2016). BMP-SMAD signaling regulates lineage priming, but is dispensable for self-renewal in mouse embryonic stem cells. STEM CELL REPORTS, 6(1), 85–94.
Chicago author-date
Gomes Fernandes, Maria, Ruben Dries, Matthias S Roost, Stefan Semrau, Ana de Melo Bernardo, Richard P Davis, Ramprasad Ramakrishnan, et al. 2016. “BMP-SMAD Signaling Regulates Lineage Priming, but Is Dispensable for Self-renewal in Mouse Embryonic Stem Cells.” Stem Cell Reports 6 (1): 85–94.
Chicago author-date (all authors)
Gomes Fernandes, Maria, Ruben Dries, Matthias S Roost, Stefan Semrau, Ana de Melo Bernardo, Richard P Davis, Ramprasad Ramakrishnan, Karoly Szuhai, Elke Maas, Lieve Umans, Vanesa Abon Escalona, Daniela Salvatori, Dieter Deforce, Wim Van Criekinge, Danny Huylebroeck, Christine Mummery, An Zwijsen, and Susana Marina Chuva de Sousa Lopes. 2016. “BMP-SMAD Signaling Regulates Lineage Priming, but Is Dispensable for Self-renewal in Mouse Embryonic Stem Cells.” Stem Cell Reports 6 (1): 85–94.
Vancouver
1.
Gomes Fernandes M, Dries R, Roost MS, Semrau S, de Melo Bernardo A, Davis RP, et al. BMP-SMAD signaling regulates lineage priming, but is dispensable for self-renewal in mouse embryonic stem cells. STEM CELL REPORTS. 2016;6(1):85–94.
IEEE
[1]
M. Gomes Fernandes et al., “BMP-SMAD signaling regulates lineage priming, but is dispensable for self-renewal in mouse embryonic stem cells,” STEM CELL REPORTS, vol. 6, no. 1, pp. 85–94, 2016.
@article{7154377,
  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.},
  author       = {Gomes Fernandes, Maria and Dries, Ruben and Roost, Matthias S and Semrau, Stefan and de Melo Bernardo, Ana and Davis, Richard P and Ramakrishnan, Ramprasad and Szuhai, Karoly and Maas, Elke and Umans, Lieve and Abon Escalona, Vanesa and Salvatori, Daniela and Deforce, Dieter and Van Criekinge, Wim and Huylebroeck, Danny and Mummery, Christine and Zwijsen, An and Chuva de Sousa Lopes, Susana Marina},
  issn         = {2213-6711},
  journal      = {STEM CELL REPORTS},
  keywords     = {EQUILIBRIUM,DEMETHYLATION,DIFFERENTIATION,HETEROGENEITY,GENE-EXPRESSION,TRANSCRIPTIONAL NETWORK,GROUND-STATE PLURIPOTENCY},
  language     = {eng},
  number       = {1},
  pages        = {85--94},
  title        = {BMP-SMAD signaling regulates lineage priming, but is dispensable for self-renewal in mouse embryonic stem cells},
  url          = {http://dx.doi.org/10.1016/j.stemcr.2015.11.012},
  volume       = {6},
  year         = {2016},
}

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