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  Different Concentrations of FGF Ligands, FGF2 or FGF8 Determine Distinct States of WNT-Induced Presomitic Mesoderm.

Sudheer, S., Liu, J., Marks, M., Koch, F., Anurin, A., Scholze, M., et al. (2016). Different Concentrations of FGF Ligands, FGF2 or FGF8 Determine Distinct States of WNT-Induced Presomitic Mesoderm. Stem Cells, 34(7), 1790-800. doi:10.1002/stem.2371.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002D-432C-F Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002D-432D-D
Genre: Journal Article

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Sudheer_et_al-2016-STEM_CELLS.pdf (Publisher version), 818KB
 
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Copyright Date:
2016-03-03
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VC AlphaMed Press 1066-5099/2016

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 Creators:
Sudheer, Smita1, 2, Author              
Liu, Jinhua1, Author
Marks, Mathias1, Author              
Koch, Frederic1, Author
Anurin, Anna1, 3, Author
Scholze, Manuela1, Author              
Senft, Anna Dorothea1, 4, Author
Wittler, Lars1, Author              
Macura, Karol1, Author              
Grote, Phillip1, 5, Author              
Herrmann, Bernhard G.1, Author              
Affiliations:
1Dept. of Developmental Genetics (Head: Bernhard G. Herrmann), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433548              
2bCentre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, The University of Edinburgh, Western General Hospital., Crewe Road, Edinburgh EH4 2XU, United Kingdom., ou_persistent22              
3cDepartment of Biology, Chemistry and Pharmacy, Free University Berlin., Berlin, Germany., ou_persistent22              
4dSir William Dunn School of Pathology, University of Oxford. , Oxford OX1 3RE, United Kingdom., ou_persistent22              
5Institute of Cardiovascular Regeneration, Center for Molecular Medicine, Goethe University, , Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Germany., ou_persistent22              

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Free keywords: Embryonic stem cells • Differentiation • Paraxial mesoderm • WNT • Brachyury • FGF • TBX6 • Mesogenin • Epiblast stem cells • CHIR99021
 Abstract: Presomitic mesoderm (PSM) cells are the precursors of the somites, which flank both sides of the neural tube and give rise to the musculo-skeletal system shaping the vertebrate body. WNT and FGF signaling control the formation of both the PSM and the somites and show a graded distribution with highest levels in the posterior PSM. We have used reporters for the mesoderm/PSM control genes T, Tbx6, and Msgn1 to investigate the differentiation of mouse ESCs from the naïve state via EpiSCs to PSM cells. Here we show that the activation of WNT signaling by CHIR99021 (CH) in combination with FGF ligand induces embryo-like PSM at high efficiency. By varying the FGF ligand concentration, the state of PSM cells formed can be altered. High FGF concentration supports posterior PSM formation, whereas low FGF generates anterior/differentiating PSM, in line with in vivo data. Furthermore, the level of Msgn1 expression depends on the FGF ligand concentration. We also show that Activin/Nodal signaling inhibits CH-mediated PSM induction in EpiSCs, without affecting T-expression. Inversely, Activin/Nodal inhibition enhances PSM induction by WNT/high FGF signaling. The ability to generate PSM cells of either posterior or anterior PSM identity with high efficiency in vitro will promote the investigation of the gene regulatory networks controlling the formation of nascent PSM cells and their switch to differentiating/somitic paraxial mesoderm.

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Language(s): eng - English
 Dates: 2015-07-302016-03-032016-04-142016-07-01
 Publication Status: Published in print
 Pages: 10
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Identifiers: DOI: 10.1002/stem.2371.
 Degree: -

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Title: Stem Cells
Source Genre: Journal
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Publ. Info: Dayton, Ohio : AlphaMed Press
Pages: 10 Volume / Issue: 34 (7) Sequence Number: - Start / End Page: 1790 - 800 Identifier: ISSN: 1066-5099
CoNE: /journals/resource/954925601690