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02501 am a22003013u 4500 |
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|a dc
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|a Przybyla, Laralynne M.
|e author
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|a Massachusetts Institute of Technology. Department of Biology
|e contributor
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|a Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
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|a Whitehead Institute for Biomedical Research
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|a Przybyla, Laralynne M.
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|a Jaenisch, Rudolf
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|a Voldman, Joel
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|a Theunissen, Thorold W.
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|a Jaenisch, Rudolf
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|a Voldman, Joel
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|a Matrix Remodeling Maintains ESC Self-Renewal by Activating Stat3
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|a Matrix Remodeling Maintains Embryonic Stem Cell Self-Renewal by Activating Stat3
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|b Wiley Blackwell,
|c 2014-10-21T15:00:38Z.
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|z Get fulltext
|u http://hdl.handle.net/1721.1/91020
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|a While a variety of natural and synthetic matrices have been used to influence embryonic stem cell (ESC) self-renewal or differentiation, and ESCs also deposit a rich matrix of their own, the mechanisms behind how extracellular matrix affects cell fate are largely unexplored. The ESC matrix is continuously remodeled by matrix metalloproteinases (MMPs), a process that we find is enhanced by the presence of mouse embryonic fibroblast feeders in a paracrine manner. Matrix remodeling by MMPs aids in the self-renewal of ESCs, as inhibition of MMPs inhibits the ability of ESCs to self-renew. We also find that addition of the interstitial collagenase MMP1 is sufficient to maintain long-term leukemia inhibitory factor (LIF)-independent mouse ESC (mESC) self-renewal in a dose-dependent manner. This remarkable ability is due to the presence of endogenously produced self-renewal-inducing signals, including the LIF-family ligand ciliary neurotrophic factor, that are normally trapped within the ECM and become exposed upon MMP-induced matrix remodeling to signal through JAK and Stat3. These results uncover a new role for feeder cells in maintaining self-renewal and show that mESCs normally produce sufficient levels of autocrine-acting pro-self-renewal ligands.
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|a National Institutes of Health (U.S.) (Grant EB007278)
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|a Singapore-MIT Alliance
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|a National Institutes of Health (U.S.) (Grant HD 045022)
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|a en_US
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|a Article
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|t Stem Cells
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