Genome-wide transcriptome analysis of integrin ß1 inhibited primed and naïve human induced pluripotent stem cells.

Cell states are governed by cell-intrinsic properties and external cues that regulate cell shape and signaling via cell-cell junctions or adhesions. Integrin ß1-mediated adhesion is dispensable in early mouse embryogenesis at pre-implantation but becomes indispensable post-implantation. This implies distinct roles for ß1-integrins in the naïve pre-implantation and primed post-implantation pluripotent stem cells (PSC). These, however, remain poorly understood. We investigated ß1-integrin control of naïve-like and primed human induced PSC (hiPSC). We find that integrin ß1 is active in naïve and primed hiPSCs and the degree of activity varies in vitro on different ECMs. Inhibition of integrin ß1 in primed hiPSCs induces naïve-like colony features, reduces actomyosin contraction and ERK activity and alters gene expression, indicative of more naïve-like features. Integrin ß1 inhibition supports epigenetic reversion of primed PSC to a naïve-like status, which involves dramatic reorganization of colony morphology, actin and adhesions. Furthermore, continued ß1 integrin inhibition facilitates the maintenance of a naïve-like state through gene expression. These data reveal unprecedented integrin-dependent regulation of PSC states and demonstrate how integrin inhibitors may help to fine-tune hiPSC function and properties in vitro. Overall design: Examination of primed and naïve hiPSCs after integrin ß1 function-blocking antibody (MAb13; anti-ß1) or IgG (control) treatment (12h in primed, 48h in naïve).