Integrin ?6?1 Expressed in ESCs Instructs the Differentiation to Endothelial Cells.

ABSTRACT: Adhesion of embryonic stem cells (ESCs) to the extracellular matrix may influence differentiation potential and cell fate decisions. Here, we investigated the inductive role of binding of integrin ?6?1 expressed in mouse (m)ESCs to laminin-1 (LN1) in mediating the differentiation of ESCs to endothelial cells (ECs). We observed that ?6?1 binding to LN1 was required for differentiation to ECs. ?6?1 functioned by recruiting the adaptor tetraspanin protein CD151, which activated FAK and Akt signaling and mediated the EC lineage-specifying transcription factor Er71. In contrast, association of the ESC-expressed ?3?1, another highly expressed LN1 binding integrin, with CD151, prevented ?6?1-mediated differentiation. CD151 thus functioned as a bifurcation router to direct ESCs toward ECs when ?6?1 associated with CD151, or prevented transition to ECs when ?3?1 associated with CD151. These observations were recapitulated in mice in which ?6 integrin or CD151 knockdown reduced the expression of Er71-regulated angiogenesis genes and development of blood vessels. Thus, interaction of ?6?1 in ESCs with LN1 activates ?6?1/CD151 signaling which programs ESCs toward the EC lineage fate.

SUBMITTER: Toya SP 

PROVIDER: S-EPMC4441581 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature