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...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2016-01-01
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| Series: | Stem Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213671115003483 |
| _version_ | 1819364692137607168 |
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| author | Maria Gomes Fernandes 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 Susana M. Chuva de Sousa Lopes |
| author_facet | Maria Gomes Fernandes 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 Susana M. Chuva de Sousa Lopes |
| author_sort | Maria Gomes Fernandes |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-24T23:02:59Z |
| format | Article |
| id | doaj.art-b277eb09b8a7405197a999545a52fb37 |
| institution | Directory Open Access Journal |
| issn | 2213-6711 |
| language | English |
| last_indexed | 2024-12-24T23:02:59Z |
| publishDate | 2016-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Stem Cell Reports |
| spelling | doaj.art-b277eb09b8a7405197a999545a52fb372022-12-21T16:35:05ZengElsevierStem Cell Reports2213-67112016-01-0161859410.1016/j.stemcr.2015.11.012BMP-SMAD Signaling Regulates Lineage Priming, but Is Dispensable for Self-Renewal in Mouse Embryonic Stem CellsMaria Gomes Fernandes0Ruben Dries1Matthias S. Roost2Stefan Semrau3Ana de Melo Bernardo4Richard P. Davis5Ramprasad Ramakrishnan6Karoly Szuhai7Elke Maas8Lieve Umans9Vanesa Abon Escalona10Daniela Salvatori11Dieter Deforce12Wim Van Criekinge13Danny Huylebroeck14Christine Mummery15An Zwijsen16Susana M. Chuva de Sousa Lopes17Department Anatomy and Embryology, Leiden University Medical Center, Leiden 2333 ZC, the NetherlandsDepartment Development and Regeneration, Laboratory of Molecular Biology (Celgen), KU Leuven, Leuven 3000, BelgiumDepartment Anatomy and Embryology, Leiden University Medical Center, Leiden 2333 ZC, the NetherlandsLeiden Institute of Physics, Leiden University, Leiden 2333 CA, the NetherlandsDepartment Anatomy and Embryology, Leiden University Medical Center, Leiden 2333 ZC, the NetherlandsDepartment Anatomy and Embryology, Leiden University Medical Center, Leiden 2333 ZC, the NetherlandsDepartment Anatomy and Embryology, Leiden University Medical Center, Leiden 2333 ZC, the NetherlandsDepartment Molecular Cell Biology, Leiden University Medical Center, Leiden 2333 ZC, the NetherlandsDepartment Human Genetics, VIB Center for the Biology of Disease, KU Leuven, Leuven 3000, BelgiumDepartment Development and Regeneration, Laboratory of Molecular Biology (Celgen), KU Leuven, Leuven 3000, BelgiumDepartment Human Genetics, VIB Center for the Biology of Disease, KU Leuven, Leuven 3000, BelgiumDepartment Anatomy and Embryology, Leiden University Medical Center, Leiden 2333 ZC, the NetherlandsLaboratory of Pharmaceutical Biotechnology, Faculty of Pharmaceutical Sciences, Ghent University, Ghent 9000, BelgiumMathematical Modelling, Statistics and Bio-informatics, Faculty Bioscience Engineering, Ghent University, Ghent 9000, BelgiumDepartment Development and Regeneration, Laboratory of Molecular Biology (Celgen), KU Leuven, Leuven 3000, BelgiumDepartment Anatomy and Embryology, Leiden University Medical Center, Leiden 2333 ZC, the NetherlandsDepartment Human Genetics, VIB Center for the Biology of Disease, KU Leuven, Leuven 3000, BelgiumDepartment Anatomy and Embryology, Leiden University Medical Center, Leiden 2333 ZC, the NetherlandsNaive 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.http://www.sciencedirect.com/science/article/pii/S2213671115003483 |
| spellingShingle | Maria Gomes Fernandes 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 Susana M. Chuva de Sousa Lopes BMP-SMAD Signaling Regulates Lineage Priming, but Is Dispensable for Self-Renewal in Mouse Embryonic Stem Cells Stem Cell Reports |
| title | 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_short | 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 |
| url | http://www.sciencedirect.com/science/article/pii/S2213671115003483 |
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