Objective To identify differentially expressed genes (DEGs) during the early stage of differentiation of human embryonic stem cells (hESCs) into insulin-producing cells (IPCs) and construct the microRNA(miRNA)-mRNA regulatory network.   Methods The datasets GSE42094 from Gene Expression Omnibus (GEO) were employed in this study and included hESCs, Diff1, Diff2, Diff3, Diff4 and IPCs groups. DEGs in the Diff1 group were selected and gene ontology(GO) and Keyoto Encyclopedia of Genes and Genomes(KEGG) pathway were deciphered. The miRNAs associated with DEGs were predicted and the miRNAmRNA regulatory network was visualized. Then the predicted miRNA was validated by paper result.   Results GO result  demonstrated that the significant term of biological process were “cell migration involved in gastrulation” and “SMAD protein signal transduction”. The KEGG pathway analysis indicated that “transformating growth factor(TGF)-beta signaling pathway” and “Signaling pathways regulating pluripotency of stem cells” played essential roles for 28 DEGs in the Diff1 group. To predict miRNA associated with DEGs, we found that miR-335-5p may regulate expressions of CDA, IFITM1, FREM1, FGF17 and ROR2 genes. There were 26 miRNAs which were validated by result  of paper.    Conclusion The miRNA-mRNA regulatory network plays an essential role during the early stage of the induction of IPCs. 

 MicroRNA, Human embryonic stem cell, Insulin-producing cell, Bioinformatics