Open AccessIntegrin α6β1 Expressed in ESC s Instructs the Differentiation to Endothelial Cells
Author(s) -
Toya Sophie P.,
Wary Kishore K.,
Mittal Manish,
Li Fei,
Toth Peter T.,
Park Changwon,
Rehman Jalees,
Malik Asrar B.
Publication year - 2015
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.1974
Subject(s) - biology , microbiology and biotechnology , embryonic stem cell , integrin , angiogenesis , gene knockdown , cellular differentiation , extracellular matrix , transcription factor , vasculogenesis , stem cell , cancer research , cell , genetics , progenitor cell , cell culture , gene
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 α6β1 expressed in mouse (m)ESCs to laminin‐1 (LN1) in mediating the differentiation of ESCs to endothelial cells (ECs). We observed that α6β1 binding to LN1 was required for differentiation to ECs. α6β1 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 α3β1, another highly expressed LN1 binding integrin, with CD151, prevented α6β1‐mediated differentiation. CD151 thus functioned as a bifurcation router to direct ESCs toward ECs when α6β1 associated with CD151, or prevented transition to ECs when α3β1 associated with CD151. These observations were recapitulated in mice in which α6 integrin or CD151 knockdown reduced the expression of Er71‐regulated angiogenesis genes and development of blood vessels. Thus, interaction of α6β1 in ESCs with LN1 activates α6β1/CD151 signaling which programs ESCs toward the EC lineage fate. S tem C ells 2015;33:1719–1729