| First Author | Toya SP | Year | 2015 |
| Journal | Stem Cells | Volume | 33 |
| Issue | 6 | Pages | 1719-29 |
| PubMed ID | 25693840 | Mgi Jnum | J:224181 |
| Mgi Id | MGI:5661641 | Doi | 10.1002/stem.1974 |
| Citation | Toya SP, et al. (2015) Integrin alpha6beta1 Expressed in ESCs Instructs the Differentiation to Endothelial Cells. Stem Cells 33(6):1719-29 |
| abstractText | 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 alpha6beta1 expressed in mouse (m)ESCs to laminin-1 (LN1) in mediating the differentiation of ESCs to endothelial cells (ECs). We observed that alpha6beta1 binding to LN1 was required for differentiation to ECs. alpha6beta1 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 alpha3beta1, another highly expressed LN1 binding integrin, with CD151, prevented alpha6beta1-mediated differentiation. CD151 thus functioned as a bifurcation router to direct ESCs toward ECs when alpha6beta1 associated with CD151, or prevented transition to ECs when alpha3beta1 associated with CD151. These observations were recapitulated in mice in which alpha6 integrin or CD151 knockdown reduced the expression of Er71-regulated angiogenesis genes and development of blood vessels. Thus, interaction of alpha6beta1 in ESCs with LN1 activates alpha6beta1/CD151 signaling which programs ESCs toward the EC lineage fate. |
