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The epigenetic modifier Fam208a is required to maintain epiblast cell fitness
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SYSNO ASEP 0486353 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title The epigenetic modifier Fam208a is required to maintain epiblast cell fitness Author(s) Bhargava, Shohag (UMG-J)
Cox, B. (CA)
Polydorou, Ch. (CZ)
Grešáková, Veronika (UMG-J)
Kořínek, Vladimír (UMG-J) RID
Strnad, Hynek (UMG-J) RID
Sedláček, Radislav (UMG-J) RID
Epp, Trevor Allan (UMG-J)
Chawengsaksophak, Kallayanee (UMG-J) ORCIDNumber of authors 9 Article number 9322 Source Title Scientific Reports. - : Nature Publishing Group - ISSN 2045-2322
Roč. 7, léto (2017)Number of pages 15 s. Language eng - English Country GB - United Kingdom Keywords bone morphogenetic protein-4 ; position-effect variegation ; gastrulating mouse embryo ; anterior-posterior axis ; mesoderm differentiation ; expression pattern ; mice lacking ; postimplantation development ; definitive endoderm ; primitive streak Subject RIV EB - Genetics ; Molecular Biology OECD category Biochemistry and molecular biology R&D Projects GA15-23165S GA ČR - Czech Science Foundation (CSF) LO1419 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) ED1.1.00/02.0109 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) ED2.1.00/19.0395 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) LM2011032 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) LM2015040 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) LQ1604 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Institutional support UMG-J - RVO:68378050 UT WOS 000408441600046 DOI 10.1038/s41598-017-09490-w Annotation Gastrulation initiates with the formation of the primitive streak, during which, cells of the epiblast delaminate to form the mesoderm and definitive endoderm. At this stage, the pluripotent cell population of the epiblast undergoes very rapid proliferation and extensive epigenetic programming. Here we show that Fam208a, a new epigenetic modifier, is essential for early post-implantation development. We show that Fam208a mutation leads to impaired primitive streak elongation and delayed epithelial-to-mesenchymal transition. Fam208a mutant epiblasts had increased expression of p53 pathway genes as well as several pluripotency-associated long non-coding RNAs. Fam208a mutants exhibited an increase in p53-driven apoptosis and complete removal of p53 could partially rescue their gastrulation block. This data demonstrates a new in vivo function of Fam208a in maintaining epiblast fitness, establishing it as an important factor at the onset of gastrulation when cells are exiting pluripotency. Workplace Institute of Molecular Genetics Contact Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Year of Publishing 2018
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