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

Autor: Mehdi Totonchi, Seyedeh-Nafiseh Hassani, Ali Sharifi-Zarchi, Natalia Tapia, Kenjiro Adachi, Julia Arand, Boris Greber, Davood Sabour, Marcos J. Araúzo-Bravo, Jörn Walter, Mohammad Pakzad, Hamid Gourabi, Hans R. Schöler, Hossein Baharvand
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: Stem Cell Reports, Vol 9, Iss 4, Pp 1275-1290 (2017)
Druh dokumentu: article
ISSN: 2213-6711
DOI: 10.1016/j.stemcr.2017.08.006
Popis: 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.
Databáze: Directory of Open Access Journals