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Updated: Sep 4, 2025

Evaluation of Injury-induced Senescence and In Vivo Reprogramming in the Skeletal Muscle
Published on: October 26, 2017
Amphiregulin mediates non-cell-autonomous effect of senescence on reprogramming
Mathieu von Joest1, Cheng Chen1, Thibaut Douché2
1Cellular Plasticity & Disease Modelling, Department of Developmental & Stem Cell Biology, CNRS UMR 3738, Institut Pasteur, 25 rue du Dr Roux, 75015 Paris, France.
Cellular senescence, a state of irreversible growth arrest, can surprisingly promote cell reprogramming. Specific factors like Amphiregulin (AREG) secreted by senescent cells enhance this process, aiding tissue repair.
Area of Science:
- Cell Biology
- Regenerative Medicine
Background:
- Cellular senescence is a stable cell cycle arrest.
- The senescence-associated secretory phenotype (SASP) influences cellular behavior.
- Senescence can impede or facilitate cell reprogramming.
Purpose of the Study:
- To investigate how paracrine senescence affects cell reprogramming.
- To identify SASP factors that promote cell fate conversion.
- To understand the role of senescence in cellular plasticity.
Main Methods:
- Induction of cellular senescence and assessment of reprogramming efficiency.
- Unbiased proteomics to identify SASP factors.
- In vitro and in vivo experiments using Amphiregulin (AREG) and skeletal muscle models.
Main Results:
- Senescence promotes in vitro reprogramming in a stress-dependent manner.
- Proteomics identified SASP factors involved in cell fate conversion.
- Amphiregulin (AREG) accelerates proliferation and mesenchymal-epithelial transition via EGFR signaling, improving reprogramming and counteracting age-related decline.
- AREG enhances in vivo reprogramming in skeletal muscle.
Conclusions:
- Cellular senescence and its SASP can facilitate cellular plasticity and reprogramming.
- AREG is a key SASP factor promoting reprogramming and tissue repair.
- Targeting SASP factors may offer therapeutic strategies for regenerative medicine.
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