BMP-SMAD Signaling Regulates Lineage Priming, but Is Dispensable for Self-Renewal in Mouse Embryonic Stem Cells
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 report...
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| Format: | Online |
| Language: | English |
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Elsevier
2015
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4720007/ |
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pubmed-47200072016-02-22 BMP-SMAD Signaling Regulates Lineage Priming, but Is Dispensable for Self-Renewal in Mouse Embryonic Stem Cells Gomes Fernandes, Maria Dries, Ruben Roost, Matthias S. Semrau, Stefan de Melo Bernardo, Ana Davis, Richard P. Ramakrishnan, Ramprasad Szuhai, Karoly Maas, Elke Umans, Lieve Abon Escalona, Vanesa Salvatori, Daniela Deforce, Dieter Van Criekinge, Wim Huylebroeck, Danny Mummery, Christine Zwijsen, An Chuva de Sousa Lopes, Susana M. Article 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. Elsevier 2015-12-17 /pmc/articles/PMC4720007/ /pubmed/26711875 http://dx.doi.org/10.1016/j.stemcr.2015.11.012 Text en © 2016 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
| 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 |
Gomes Fernandes, Maria Dries, Ruben Roost, Matthias S. Semrau, Stefan de Melo Bernardo, Ana Davis, Richard P. Ramakrishnan, Ramprasad Szuhai, Karoly Maas, Elke Umans, Lieve Abon Escalona, Vanesa Salvatori, Daniela Deforce, Dieter Van Criekinge, Wim Huylebroeck, Danny Mummery, Christine Zwijsen, An Chuva de Sousa Lopes, Susana M. |
| spellingShingle |
Gomes Fernandes, Maria Dries, Ruben Roost, Matthias S. Semrau, Stefan de Melo Bernardo, Ana Davis, Richard P. Ramakrishnan, Ramprasad Szuhai, Karoly Maas, Elke Umans, Lieve Abon Escalona, Vanesa Salvatori, Daniela Deforce, Dieter Van Criekinge, Wim Huylebroeck, Danny Mummery, Christine Zwijsen, An Chuva de Sousa Lopes, Susana M. BMP-SMAD Signaling Regulates Lineage Priming, but Is Dispensable for Self-Renewal in Mouse Embryonic Stem Cells |
| author_facet |
Gomes Fernandes, Maria Dries, Ruben Roost, Matthias S. Semrau, Stefan de Melo Bernardo, Ana Davis, Richard P. Ramakrishnan, Ramprasad Szuhai, Karoly Maas, Elke Umans, Lieve Abon Escalona, Vanesa Salvatori, Daniela Deforce, Dieter Van Criekinge, Wim Huylebroeck, Danny Mummery, Christine Zwijsen, An Chuva de Sousa Lopes, Susana M. |
| author_sort |
Gomes Fernandes, Maria |
| title |
BMP-SMAD Signaling Regulates Lineage Priming, but Is Dispensable for Self-Renewal in Mouse Embryonic Stem Cells |
| title_short |
BMP-SMAD Signaling Regulates Lineage Priming, but Is Dispensable for Self-Renewal in Mouse Embryonic Stem Cells |
| title_full |
BMP-SMAD Signaling Regulates Lineage Priming, but Is Dispensable for Self-Renewal in Mouse Embryonic Stem Cells |
| title_fullStr |
BMP-SMAD Signaling Regulates Lineage Priming, but Is Dispensable for Self-Renewal in Mouse Embryonic Stem Cells |
| title_full_unstemmed |
BMP-SMAD Signaling Regulates Lineage Priming, but Is Dispensable for Self-Renewal in Mouse Embryonic Stem Cells |
| title_sort |
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. |
| publisher |
Elsevier |
| publishDate |
2015 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4720007/ |
| _version_ |
1613526277674762240 |