Adhesion, but not a specific cadherin code, is indispensable for ES cell and induced pluripotency

Bedzhov I., Alotaibi H., Basilicata M. F., Ahlborn K., Liszewska E., Brabletz T., ...More

STEM CELL RESEARCH, vol.11, no.3, pp.1250-1263, 2013 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 11 Issue: 3
  • Publication Date: 2013
  • Doi Number: 10.1016/j.scr.2013.08.009
  • Journal Name: STEM CELL RESEARCH
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.1250-1263
  • Dokuz Eylül University Affiliated: No


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. (C) 2013 Elsevier B.V. All rights reserved.