Effects Of Epidermal Growth Factor Receptor Deficiency On Self-renewal And Pluripotency Of Mouse Embryonic Stem Cells

Self-renewal and pluripotency are considered as unwavering features of embryonic stem cells(ESCs).How ESCs regulate the self-renewal and differentiation is a central question in development and regenerative medicine research.Epidermal growth factor receptor(EGFR)was identified as a critical regulator in cancer stem cells,but its role in the maintenance of ESCs is poorly understood.Here we show that EGFR disruption by its specific inhibitor AG1478 impaired self-renewal and pluripotency in mouse ESCs(mESCs).EGFR inhibition in mESCs markedly reduced cell proliferation,caused cell cycle arrest at Go/Gi phase,and altered expressions of the cell cycle regulatory genes.The expressions of pluripotency factors also dramatically decreased,while the differentiation related genes were up regulated in mESCs after EGFR inhibition.Moreover,EGFR inhibition in mESCs impaired embryoid body(EB)formation,indicating its impaired pluripotency.RNA-seq analysis displayed that after EGFR inhibition by AG1478 transcript profiling was changed significantly,and a large number of differentially expressed genes were involved in cell cycle,apoptotic process,epigenetic modification,and metabolic process,which were related to self-renewal and pluripotency,confirming that EGFR deficiency impaired self-renewal and pluripotency in mESCs.Our results demonstrated the importance of EGFR in guarding the sternness of mESCs.