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

Matrix remodeling maintains embryonic stem cell self-renewal by activating Stat3.
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DOI:
10.1002/stem.1360
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发表时间:
2013-06
期刊:
影响因子:
5.2
通讯作者:
Voldman, Joel
Voldman, Joel
中科院分区:
医学2区
文献类型:
--
作者:
Przybyla, Laralynne M.;Theunissen, Thorold W.;Jaenisch, Rudolf;Voldman, Joel

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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 LIF-independent 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 CNTF, 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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期刊: PloS one
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影响因子: --
作者:
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