RT Journal Article
SR Electronic
T1 Chemically Induced Senescence in Human Stem Cell-Derived Neurons Promotes Phenotypic Presentation of Neurodegeneration
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.07.11.451956
DO 10.1101/2021.07.11.451956
A1 Ali Fathi
A1 Sakthikumar Mathivanan
A1 Linghai Kong
A1 Andrew J Petersen
A1 Cole R. K. Harder
A1 Jasper Block
A1 Julia Marie Miller
A1 Anita Bhattacharyya
A1 Daifeng Wang
A1 Su-Chun Zhang
YR 2021
UL http://biorxiv.org/content/early/2021/07/12/2021.07.11.451956.abstract
AB Modeling age-related neurodegenerative disorders with human stem cells is 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.Competing Interest StatementThe authors have declared no competing interest.