The role of signaling pathways in derivation and maintenance of mouse embryonic stem cells

Stem cells are believed as the premier hope to regenerate the defected tissues. In this regard, enhancing the efficient derivation of mouse embryonic stem (ES) cells, as the best model of pluripotent stem cell, facilitates capturing of the efficient derivation of human ES cells. Small molecules play a critical role in improving the efficiency of generating the pluripotent stem cells by inhibiting signaling pathways related to differentiation. This study aimed to evaluate the role of some molecular signaling pathways (e.g. JAK/STAT, MAPK/ERK, PI3K/AKT, WNT/GSK3 and TGF-β) in the cells involved in producing and maintaining ES cells. In this review study, the relevant articles to signaling pathways and embryonic stem cells were selected from PubMed database. In addition, the procedure for the efficient derivation of mouse ES cells was analyzed using small molecules under different conditions, like 2i and R2i culture. The R2i culture condition increases the efficiency of generation and maintenance of ES cell lines from different types of mouse strain. Thus, findings showed that by inhibiting the MEK and TGF-β pathways in this process, the higher frequency of cells would be maintained at ground state of pluripotency with no differentiation. To understand the molecular effects of R2i culture condition on enhancing the efficiency of generating the mouse ES cells, the assessment of key pluripotency and differentiation gene expressions as well as the epigenetic changes within the ES cell derivation process seems to be essential.