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Title: BMP-SMAD Signaling Regulates Lineage Priming, but Is Dispensable for Self-Renewal in Mouse Embryonic Stem Cells
Authors: 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 #
Issue Date: Jan-2016
Publisher: Cell Press
Series Title: Stem Cell Reports vol:6 issue:1 pages:85-94
Article number: S2213-6711(15)00348-3
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.
URI: 
ISSN: 2213-6711
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Human Genetics - miscellaneous
Stem Cell Biology and Embryology (+)
Laboratory of Developmental Signaling
× corresponding author
# (joint) last author

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