544049  Pyrintegrin

Ptn, N-(Cyclopropylmethyl)-4-(4-(6-hydroxy-3,4-dihydroquinolin-1(2H)-yl)pyrimidin-2-ylamino)benzenesulfonamide, β1 Integrin Activator

A cell-permeable pyrimidine compound that promotes the adhesion of individually dissociated hESCs on matrigel- or laminin-, but not gelatin-coated surfaces and substantially reduces trypsinization-induced apoptosis (10% vs 81% TUNEL-positive cells from 2 µM Ptn or DMSO control matrigel cultures, respectively, after trypsinization), while maintaining cells’ self-renewal ability (colony formation rate = 25% or 1% 4 d after low density seeding of single-cells on matrigel surface with 2 µM Ptn or DMSO control, respectively) and the pluripotency of expanded cultures for more than 40 passages. Ptn treatment is shown to induce the activation of β1 integrin and multiple growth factor receptors, including FGFR1, IGFR1, EGFR1, and ErbB2, while blockage of β1 integrin, PI 3-K, or growth factor receptors abolishes the survival promoting effect of Ptn. Single-cell dissociation is demonstrated to hyperactivate Rho-ROCK signaling, while efficient hESC-ECM interaction suppresses Rho-Rock activation, resulting in the stabilization of newly synthesized cell surface E-cadherin, which in turn promotes cell-cell adhesion, an important determinant of hESC survival.