Skip to Content
MilliporeSigma
  • Amphiregulin mediates non-cell-autonomous effect of senescence on reprogramming.

Amphiregulin mediates non-cell-autonomous effect of senescence on reprogramming.

Cell reports (2022-07-14)
Mathieu von Joest, Cheng Chen, Thibaut Douché, Jeremy Chantrel, Aurélie Chiche, Quentin Giai Gianetto, Mariette Matondo, Han Li
ABSTRACT

Cellular senescence is an irreversible growth arrest with a dynamic secretome, termed the senescence-associated secretory phenotype (SASP). Senescence is a cell-intrinsic barrier for reprogramming, whereas the SASP facilitates cell fate conversion in non-senescent cells. However, the mechanisms by which reprogramming-induced senescence regulates cell plasticity are not well understood. Here, we investigate how the heterogeneity of paracrine senescence impacts reprogramming. We show that senescence promotes in vitro reprogramming in a stress-dependent manner. Unbiased proteomics identifies a catalog of SASP factors involved in the cell fate conversion. Amphiregulin (AREG), frequently secreted by senescent cells, promotes in vitro reprogramming by accelerating proliferation and the mesenchymal-epithelial transition via EGFR signaling. AREG treatment diminishes the negative effect of donor age on reprogramming. Finally, AREG enhances in vivo reprogramming in skeletal muscle. Hence, various SASP factors can facilitate cellular plasticity to promote reprogramming and tissue repair.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Puromycin dihydrochloride from Streptomyces alboniger, powder, BioReagent, suitable for cell culture
Sigma-Aldrich
Bovine Serum Albumin, lyophilized powder, ≥96% (agarose gel electrophoresis)
Millipore
Phosphatase Inhibitor Cocktail Set II, A cocktail of five phosphatase inhibitors for the inhibition of acid and alkaline phosphatases as well as protein tyrosine phosphatases (PTPs). Suitable for use with cell lysates and tissue extracts.
Sigma-Aldrich
Protease Inhibitor Cocktail Set I, A cocktail of five protease inhibitors that will inhibit a broad range of proteases and esterases. Supplied with a data sheet.