LKB1 controls the pluripotent state of human embryonic stem cells.

Human embryonic stem cells maintained on human amniotic epithelial cells (hESCs(hAEC)) are better preserved in an undifferentiated state and express pluripotency genes Oct4, Nanog, and Sox2 at higher levels compared with growth on mitotically inactivated mouse embryonic fibroblasts (hESCs(MEF)). Here we report that this correlates with the absence of the tumor suppressor and metabolic balancer gene, LKB1 expression in hESCs(hAEC). RNA interference knockdown of LKB1 in hESCs(MEF) resulted in upregulation of pluripotency marker genes of Oct4 and Nanog, while downregulation of differentiation markers (Runx1, AFP, GATA, Brachyury, Sox17 and Nestin). As in somatic cells, LKB1 controls p21/WAF1 expression by promoter binding in hESCs(MEF). Our results suggested that the absence of LKB1-mediated signaling is an important determinant of feeder cell-mediated support of hESC renewal.