title: Adhesion, but not a specific cadherin code, is indispensable for ES cell and induced pluripotency.
abstract: Embryonic stem (ES) cell pluripotency and induced pluripotent stem (iPS) cell generation is dependent on a core transcriptional network and proper cell-cell adhesion mediated by E-cadherin (E-cad). Whereas E-cad is associated with pluripotency, N-cadherin (N-cad) expression is correlated with differentiation into mesodermal and neuroectodermal lineages. We investigated whether E-cad harbors unique molecular features in establishing or maintaining pluripotency. By using a gene replacement knock-in (ki) approach to express N-cadherin (N-cad) or E-cad/N-cad chimeric cadherins under the control of the E-cad locus, we show that all E-cad-depleted ki/ki ES cells are maintained in an undifferentiated state. Surprisingly, these cells retained key features of pluripotency, such as Nanog expression and full differentiation capacity in vitro and in vivo, whereas E-cad knockout (ko) ES cells irreversibly lost most of these features. Moreover, our results indicate that E-cad mediated adhesion is essential for iPS cell generation, since E-cad depleted fibroblasts were not reprogrammed. In contrast, N-cad efficiently supports somatic reprogramming similar to E-cad, and permits initiation of the crucial initial step of mesenchymal-epithelial transition. Thus, we show that cell adhesion and a robust pluripotent phenotype are ultimately connected. Since N-cad properly compensates for loss of E-cad, no specific 'cadherin code' is required.
authors.affiliation: Department of Molecular Embryology, Max-Planck Institute of Immunobiology and Epigenetics, Stuebeweg 51, D-79108 Freiburg, Germany; Wellcome Trust/Cancer Research UK Gurdon Institute, Tennis Court Road, Cambridge CB2 1QN, UK.
authors.forename: Ivan
authors.initials: I
authors.lastname: Bedzhov
authors.forename: Hani
authors.initials: H
authors.lastname: Alotaibi
authors.forename: M Felicia
authors.initials: MF
authors.lastname: Basilicata
authors.forename: Kerstin
authors.initials: K
authors.lastname: Ahlborn
authors.forename: Ewa
authors.initials: E
authors.lastname: Liszewska
authors.forename: Thomas
authors.initials: T
authors.lastname: Brabletz
authors.forename: Marc P
authors.initials: MP
authors.lastname: Stemmler
mesh_terms: D000818:Animals; D015820:Cadherins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion; D002454:Cell Differentiation; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D055879:Gene Knock-In Techniques; D056426:Genetic Loci; D018398:Homeodomain Proteins / Q000378:metabolism; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D000071317:Nanog Homeobox Protein; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D015820:Cadherins; D018398:Homeodomain Proteins; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D011993:Recombinant Fusion Proteins