Human embryonic stem cells (hESs) and adipose-derived stem cells (hADSCs) are able to differentiate into hepatocytes. However, a role of Wnt signaling in hepatic differentiation of stem cells is unclear. This study characterized the transcriptional expression pattern of Wnt signaling genes during the sequential hepatocytes differentiation of hES and hADSC. The sequential hepatocytes differentiation of hES and hADSC was induced by three steps including induction, differentiation and maturation steps with the treatment of cytokines. Hepatocytes differentiation was more efficient in hES than hADSC in terms of the expression of hepatocyte-specific genes and the cellular uptake of ICG. The expression of WNT2B, WNT5A, and WISP1 increased at late hepatic differentiation of hES, but the expression of DKK1 and CCND1 decreased during early hepatic differentiation of hES. During hepatic differentiation of hADSC, the expression of WNT2B and WISP1 decreased, but the expression of WNT5B and DKK1 increased at late hepatic differentiation. These results showed that Wnt signaling appears to be activated in hepatic differentiation of hES, but repressed in hepatic differentiation of hADSC in a time-dependent manner, which suggests the differential regulation of Wnt signaling for hepatic differentiation of hES and hADSC. (c) 2013 Elsevier Inc. All rights reserved.