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