title: LKB1 controls the pluripotent state of human embryonic stem cells.
abstract: 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.
authors.affiliation: The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, People's Republic of China. laidongmei@hotmail.com
authors.forename: Dongmei
authors.initials: D
authors.lastname: Lai
authors.forename: Yifei
authors.initials: Y
authors.lastname: Chen
authors.forename: Fangyuan
authors.initials: F
authors.lastname: Wang
authors.forename: Lizhen
authors.initials: L
authors.lastname: Jiang
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Wei
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D061252:Feeder Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D039904:Pluripotent Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D034741:RNA, Small Interfering / Q000494:pharmacology
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D034741:RNA, Small Interfering; D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases