Blockage of the Epithelial-to-Mesenchymal Transition Is Required for Embryonic Stem Cell Derivation

Stem Cell Reports

Hamid Gourabi¹  Hossein Baharvand²  Seyedeh-Nafiseh Hassani²  Mohammad Pakzad²  Ali Sharifi-Zarchi²  Mehdi Totonchi²  Davood Sabour²  Marcos J. Araúzo-Bravo³  Natalia Tapia⁴  Boris Greber⁵  Kenjiro Adachi⁵  Hans R. Schöler⁵  Julia Arand⁶  Jörn Walter⁶ 

[1] Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran;Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran;Group of Computational Biology and Systems Biomedicine, Biodonostia Health Research Institute, 20014 San Sebastián, Spain;Institute of Biomedicine of Valencia, Spanish National Research Council, Jaime Roig 11, 46010 Valencia, Spain;Max Planck Institute for Molecular Biomedicine, Röntgenstrasse 20, 48149 Münster, Germany;University of Saarland, FR 8.3, Biological Sciences, Genetics/Epigenetics, Campus A2.4, 66123 Saarbrücken, Germany;

关键词: mouse;    ESC derivation;    EMT;   

DOI  :  10.1016/j.stemcr.2017.08.006

来源: DOAJ

【 摘 要 】

Pluripotent cells emanate from the inner cell mass (ICM) of the blastocyst and when cultivated under optimal conditions immortalize as embryonic stem cells (ESCs). The fundamental mechanism underlying ESC derivation has, however, remained elusive. Recently, we have devised a highly efficient approach for establishing ESCs, through inhibition of the MEK and TGF-β pathways. This regimen provides a platform for dissecting the molecular mechanism of ESC derivation. Via temporal gene expression analysis, we reveal key genes involved in the ICM to ESC transition. We found that DNA methyltransferases play a pivotal role in efficient ESC generation. We further observed a tight correlation between ESCs and preimplantation epiblast cell-related genes and noticed that fundamental events such as epithelial-to-mesenchymal transition blockage play a key role in launching the ESC self-renewal program. Our study provides a time course transcriptional resource highlighting the dynamics of the gene regulatory network during the ICM to ESC transition.

【 授权许可】

Unknown