Chemically induced senescence in human stem cell-derived neurons promotes phenotypic presentation of neurodegeneration.
cell senescence
disease modeling
neural differentiation
neurodegeneration
Journal
Aging cell
ISSN: 1474-9726
Titre abrégé: Aging Cell
Pays: England
ID NLM: 101130839
Informations de publication
Date de publication:
01 2022
01 2022
Historique:
revised:
18
11
2021
received:
08
07
2021
accepted:
10
12
2021
pubmed:
26
12
2021
medline:
30
3
2022
entrez:
25
12
2021
Statut:
ppublish
Résumé
Modeling age-related neurodegenerative disorders with human stem cells are difficult due to the embryonic nature of stem cell-derived neurons. We developed a chemical cocktail to induce senescence of iPSC-derived neurons to address this challenge. We first screened small molecules that induce embryonic fibroblasts to exhibit features characteristic of aged fibroblasts. We then optimized a cocktail of small molecules that induced senescence in fibroblasts and cortical neurons without causing DNA damage. The utility of the "senescence cocktail" was validated in motor neurons derived from ALS patient iPSCs which exhibited protein aggregation and axonal degeneration substantially earlier than those without cocktail treatment. Our "senescence cocktail" will likely enhance the manifestation of disease-related phenotypes in neurons derived from iPSCs, enabling the generation of reliable drug discovery platforms.
Identifiants
pubmed: 34953016
doi: 10.1111/acel.13541
pmc: PMC8761019
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13541Subventions
Organisme : NICHD NIH HHS
ID : P01 HD076892
Pays : United States
Organisme : NINDS NIH HHS
ID : R24 NS086604
Pays : United States
Organisme : NIMH NIH HHS
ID : P50 MH100031
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS096282
Pays : United States
Organisme : NICHD NIH HHS
ID : U54 HD090256
Pays : United States
Informations de copyright
© 2021 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.
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