Remodeling of cytoskeleton, chromatin, and gene expression during mechanical rejuvenation of aged human dermal fibroblasts
Name
remodeling-of-cytoskeleton-chromatin-and-gene-expression-during-mechanical-rejuvenation-of-aged-human-dermal-fibroblasts.pdf
Description
Published version
Size
5.11 MB
Format
Adobe PDF
Checksum (MD5)
b1c80d949dc6f771f573687504f19821
Author(s)
Sornapudi, Trinadha Rao
Yuan, Luezhen
Braunger, Jana M
Uhler, Caroline
Shivashankar, GV
Date Issued
January 1, 2025
Journal
Molecular Biology of the Cell
Publisher
American Society for Cell Biology (ASCB)
Citation
Sornapudi, Trinadha Rao, Yuan, Luezhen, Braunger, Jana M, Uhler, Caroline and Shivashankar, GV. 2025. "Remodeling of cytoskeleton, chromatin, and gene expression during mechanical rejuvenation of aged human dermal fibroblasts." Molecular Biology of the Cell, 36 (1).
Version
Final published version
Abstract
Aging is associated with a progressive decline in cellular function. To reset the aged cellular phenotype, various reprogramming approaches, including mechanical routes, have been explored. However, the epigenetic mechanisms underlying cellular rejuvenation are poorly understood. Here, we studied the cytoskeletal, genome-wide chromatin and transcriptional changes in young, aged, and mechanically rejuvenated fibroblasts using immunofluorescence, RNA sequencing, and Hi-C experiments. The mechanically rejuvenated aged fibroblasts, that had partially reset their transcription to a younger cell state, showed a local reorganization of the interchromosomal contacts and lamina-associated domains. Interestingly, the observed chromatin reorganization correlated with the transcriptional changes. Immunofluorescence experiments in the rejuvenated state confirmed increased actomyosin contractility like younger fibroblasts. In addition, the rejuvenated contractile properties were maintained over multiple cell passages. Overall, our results give an overview of how changes in the cytoskeleton, chromatin, and gene activity are connected to aging and rejuvenation.
MIT Department
Broad Institute of MIT and Harvard
Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
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Creative Commons Attribution-Noncommercial-ShareAlike
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DOI of Published Version
https://doi.org/10.1091/mbc.E24-09-0430
