Adhesion, but not a specific cadherin code, is indispensable for ES cell and induced pluripotency.
Stem Cell Res, 2013/11;11(3):1250-63.
Bedzhov I[1], Alotaibi H, Basilicata MF, Ahlborn K, Liszewska E, Brabletz T, Stemmler MP
Affiliations
PMID: 24036274
Impact factor: 1.587
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.
MeSH terms
Animals; Cadherins; Cell Adhesion; Cell Differentiation; Cells, Cultured; Embryonic Stem Cells; Epithelial-Mesenchymal Transition; Gene Knock-In Techniques; Genetic Loci; Homeodomain Proteins; Induced Pluripotent Stem Cells; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Nude; Nanog Homeobox Protein; Recombinant Fusion Proteins
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