Novel insights from a multiomics dissection of the Hayflick limit.
chromosomes
epithelial to mesenchymal transition
gene expression
genetics
genomics
human
myofibroblast
replicative senescence
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
04 02 2022
04 02 2022
Historique:
received:
12
05
2021
accepted:
31
01
2022
pubmed:
5
2
2022
medline:
30
4
2022
entrez:
4
2
2022
Statut:
epublish
Résumé
The process wherein dividing cells exhaust proliferative capacity and enter into replicative senescence has become a prominent model for cellular aging in vitro. Despite decades of study, this cellular state is not fully understood in culture and even much less so during aging. Here, we revisit Leonard Hayflick's original observation of replicative senescence in WI-38 human lung fibroblasts equipped with a battery of modern techniques including RNA-seq, single-cell RNA-seq, proteomics, metabolomics, and ATAC-seq. We find evidence that the transition to a senescent state manifests early, increases gradually, and corresponds to a concomitant global increase in DNA accessibility in nucleolar and lamin associated domains. Furthermore, we demonstrate that senescent WI-38 cells acquire a striking resemblance to myofibroblasts in a process similar to the epithelial to mesenchymal transition (EMT) that is regulated by t YAP1/TEAD1 and TGF-β2. Lastly, we show that verteporfin inhibition of YAP1/TEAD1 activity in aged WI-38 cells robustly attenuates this gene expression program.
Identifiants
pubmed: 35119359
doi: 10.7554/eLife.70283
pii: 70283
pmc: PMC8933007
doi:
pii:
Banques de données
GEO
['GSE175533', 'GSE58910', 'GSE78043', 'GSE49341']
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2022, Chan et al.
Déclaration de conflit d'intérêts
MC, HY, IS, TM, RW, AI, JO, JG, LC, TV, AF, CK, BB, FM, DK, MR, RC, AL, DB, DH is affiliated with Calico Life Sciences, LLC. The author has no other competing interests to declare
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