Generation of a conditional cellular senescence model using proximal tubule cells and fibroblasts from human kidneys.
Journal
Cell death discovery
ISSN: 2058-7716
Titre abrégé: Cell Death Discov
Pays: United States
ID NLM: 101665035
Informations de publication
Date de publication:
14 Aug 2024
14 Aug 2024
Historique:
received:
13
02
2024
accepted:
01
08
2024
revised:
26
07
2024
medline:
15
8
2024
pubmed:
15
8
2024
entrez:
14
8
2024
Statut:
epublish
Résumé
Emerging evidence highlights cellular senescence's pivotal role in chronic kidney disease (CKD). Proximal tubule epithelial cells (PTECs) and fibroblasts are major players in CKD and serve as cellular sources of senescence. The generation of a conditionally immortalized human kidney cell model would allow to better understand the specific mechanisms and factors associated with cellular senescence in a controlled setting, devoid of potential confounding factors such as age and comorbidities. In addition, the availability of human kidney cell lines for preclinical research is sparse and most cell lines do not reflect their in vivo counterparts due to their altered behavior as immortalized cancer-like cells. In this study, PTECs and fibroblasts from human kidneys were isolated and transduced with doxycycline-inducible simian virus 40 large T antigen (SV40LT) vector. By comparing their gene expression with single-cell RNA sequencing data from human kidneys, the newly produced human kidney cell lines demonstrated significant resemblances to their in vivo counterparts. As predicted, PTECs showed functional activity and fibroblasts responded to injury with fibrosis. Withdrawal of the immortalizing factor doxycycline led to p21
Identifiants
pubmed: 39143064
doi: 10.1038/s41420-024-02131-y
pii: 10.1038/s41420-024-02131-y
doi:
Types de publication
Journal Article
Langues
eng
Pagination
364Subventions
Organisme : Else Kröner-Fresenius-Stiftung (Else Kroner-Fresenius Foundation)
ID : 2022_EKES.03
Organisme : CSC | Chinese Government Scholarship
ID : 202008230182
Organisme : CSC | Chinese Government Scholarship
ID : 202008080170
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : 445703531
Organisme : European Cooperation in Science and Technology (COST)
ID : 21165
Informations de copyright
© 2024. The Author(s).
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