Endogenous suppression of WNT signalling in human embryonic stem cells leads to low differentiation propensity towards definitive endoderm

We compared a transcriptome of hESC line VUB04 which has a low differentiation propensity towards definitive endoderm with transcriptomes of control hESC lines at the undifferentiated stage and after the 24-hour differentiation towards mesendoderm. The results showed that endogenous suppression of WNT signalling in VUB04 results in an inefficient switch from self-renewal to commitment during the definitive endoderm differentiation. Subsequenlty, we demonstrated that this differentiation disruption can be overcome by increasing the WNT stimulation or by inhibiting the PI3K/AKT signalling at the onset of differentiation. Four experimental groups (1- undifferentiated VUB01, VUB02 and VUB03, 2- undifferentiated VUB04, 3- 24h mesendoderm VUB01 and VUB02, 4- 24h mesendoderm VUB04); each experimental group conists of at least 5 samples/replicates; group 1 was compared to group 2, group 3 was compared to group 4.