Matrix remodeling maintains embryonic stem cell self-renewal by activating Stat3

Laralynne M. Przybyla, Thorold W. Theunissen, Rudolf Jaenisch, Joel Voldman

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


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.

Original languageEnglish
Pages (from-to)1097-1106
Number of pages10
Issue number6
StatePublished - Jun 2013


  • Embryonic stem cell
  • Extracellular matrix
  • Matrix metalloproteinase
  • Self-renewal
  • Stat3


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