Matrix Remodeling Maintains ESC Self-Renewal by Activating Stat3
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Voldman_Matrix remodeling.pdf
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Author(s)
Przybyla, Laralynne M.
Theunissen, Thorold W.
Jaenisch, Rudolf
Voldman, Joel
Alternative Title
Matrix Remodeling Maintains Embryonic Stem Cell Self-Renewal by Activating Stat3
Date Issued
May 2013
Journal
Stem Cells
Publisher
Wiley Blackwell
Citation
Przybyla, Laralynne M., Thorold W. Theunissen, Rudolf Jaenisch, and Joel Voldman. “Matrix Remodeling Maintains Embryonic Stem Cell Self-Renewal by Activating Stat3.” STEM CELLS 31, no. 6 (May 22, 2013): 1097–1106.
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Author's final manuscript
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
Whitehead Institute for Biomedical Research
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DOI of Published Version
https://doi.org/10.1002/stem.1360
