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

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. •Transcriptome data indicated a dynamic gene expression during ICM-ESC transition•DNA methyltransferases play a prominent role in efficient ESC generation•ESCs maintain pre-Epiblast cell identity•EMT blockage is required for ESC derivation In this article, Baharvand and colleagues provided a platform to discover influential genes and cellular events involved in transition from the ICM cells to embryonic stem cells (ESCs) by applying gene expression profiling from the ICM cells, various stages of ICM outgrowths, and early to further passages of ESCs.