Engineering integrin signaling for promoting embryonic stem cell self-renewal in a precisely defined niche
| Autor: | Yun Suk Jo, Seung Tae Lee, Jeffrey A. Hubbell, Jong Eun Ihm, Jung Im Yun, Stephan Kontos, Jeong Mook Lim, Mayumi Mochizuki, André J. van der Vlies |
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| Rok vydání: | 2009 |
| Předmět: |
Homeobox protein NANOG
Integrins Integrin Biophysics Cell Culture Techniques Alpha (ethology) Bioengineering Cell Communication Protein Engineering CD49c Cell Line Biomaterials Mice Biomimetic Materials Materials Testing Animals Beta (finance) Embryonic Stem Cells Cell Proliferation biology Tissue Engineering Hydrogels Cell biology Extracellular Matrix Fibronectin Genetic Enhancement Mechanics of Materials embryonic structures Ceramics and Composites biology.protein Integrin beta 6 Stem cell |
| Zdroj: | Biomaterials. 31(6) |
| ISSN: | 1878-5905 |
| Popis: | 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 alpha(5)beta(1), alpha(v)beta(5), alpha(6)beta(1) and alpha(9)beta(1) play important roles in maintenance of stemness in undifferentiated mouse ESCs. Using the well-defined matrix as a tool to activate integrins alpha(5)beta(1) plus alpha(v)beta(5), alpha(6)beta(1) and alpha(9)beta(1), 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. |
| Databáze: | OpenAIRE |
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