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Engineering integrin signaling for promoting embryonic stem cell self-renewal in a precisely defined niche

Paper ID Volume ID Publish Year Pages File Format Full-Text
9825 648 2010 8 PDF Available
Title
Engineering integrin signaling for promoting embryonic stem cell self-renewal in a precisely defined niche
Abstract

We present development and use of a 3D synthetic extracellular matrix (ECM) analog with integrin-specific adhesion ligands to characterize the microenvironmental influences in embryonic stem cell (ESC) self-renewal. Transcriptional analysis of 24 integrin subunits followed by confirmation at the translational and functional levels suggested that integrins α5β1, αvβ5, α6β1 and α9β1 play important roles in maintenance of stemness in undifferentiated mouse ESCs. Using the well-defined matrix as a tool to activate integrins α5β1 plus αvβ5, α6β1 and α9β1, individually and in combination, differential integrin activation was demonstrated to exert exquisite control over ESC fate decisions. Simultaneous ligation of these four integrin heterodimers promoted self-renewal, as evidence by prolonged SSEA-1, Oct4 and Nanog expression, and induced Akt1 kinase signaling along with translational regulation of other stemness-related genes. The biofunctional network we have designed based on this knowledge may be useful as a defined niche for regulating ESC pluripotency through selective cell–matrix interactions, and the method we present may be more generally useful for probing matrix interactions in stem cell self-renewal and differentiation.

Keywords
Adhesion molecule; Cell signaling; ECM (extracellular matrix); Hydrogel; Stem cell
First Page Preview
Engineering integrin signaling for promoting embryonic stem cell self-renewal in a precisely defined niche
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 31, Issue 6, February 2010, Pages 1219–1226
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering