Notch activation shifts the fate decision of senescent progenitors toward myofibrogenesis in human adipose tissue.

ABSTRACT: Senescence is a key event in the impairment of adipose tissue (AT) function with obesity and aging but the underlying molecular and cellular players remain to be fully defined, particularly with respect to the human AT progenitors. We have found distinct profiles of senescent progenitors based on AT location between stroma from visceral versus subcutaneous AT. In addition to flow cytometry, we characterized the location differences with transcriptomic and proteomic approaches, uncovering the genes and developmental pathways that are underlying replicative senescence. We identified key components to include INBHA as well as SFRP4 and GREM1, antagonists for the WNT and BMP pathways, in the senescence-associated secretory phenotype and NOTCH3 in the senescence-associated intrinsic phenotype.

SUBMITTER: Boulet N 

PROVIDER: S-EPMC10014050 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature