Aim:  Human embryonic stem cells (hESCs) are able to self‐renew and differentiate into a variety of cell types. Although miRNAs have emerged as key regulators in the cellular process, a few studies have been reported about behaviors of miRNAs during differentiation of hESCs into a specialized cell type. Here, we demonstrate that different kinds of miRNAs may function in a lineage‐specific manner during the differentiation of human embryonic stem cells (hESCs).

Methods:  hESCs were induced to definitive endoderm (DE) cells and further differentiated to hepatocytes. The expression levels of miRNAs were examined in hESCs, DE cells, and hepatocytes by miRNA array using 799 human miRNA probes.

Results:  Among 387 miRNAs significantly detected, 13 and 56 miRNAs were downregulated and upregulated during transition of hESCs to DE cells, respectively, while 30 and 92 miRNAs were downregulated and upregulated during differentiation of DE cells to hepatocytes, respectively. In particular, 5, 4, and 86 miRNAs were enriched in hESCs, DE cells, and hepatocytes, respectively. Quantitative RT‐PCR represented that miR‐512‐3p, miR‐512‐5p and miR‐520c‐3p were enriched in hESCs, miR‐9*, miR‐205 and miR‐375 in hESC‐derived DE cells, and miR‐10a, miR‐122 and miR‐21 in hESC‐derived hepatocytes. Expression patterns of lineage‐specific miRNAs in the liver tissue were similar to those of hESC‐derived hepatocytes.

Conclusion:  The results indicate that different kinds of miRNAs may function in a lineage‐specific manner during differentiation of hESCs into a specialized cell type.