Remodeling of cytoskeleton, chromatin, and gene expression during mechanical rejuvenation of aged human dermal fibroblasts

• DOI: 10.1091/mbc.e24-09-0430
• Publication Date: 2024-12-04T18:22:36Z
• Authors: Trinadha Rao Sorn...; Luezhen Yuan; Jana M. Braunger; Caroline Uhler; G.V. Shivashankar
• Keywords: Reprogramming; Nuclear lamina

Aging is associated with a progressive decline in cellular function. To reset the aged phenotype, various reprogramming approaches, including mechanical routes, have been explored. However, epigenetic mechanisms underlying rejuvenation are poorly understood. Here, we studied cytoskeletal, genome-wide chromatin and transcriptional changes young, mechanically rejuvenated fibroblasts using immunofluorescence, RNA-seq Hi-C experiments. The fibroblasts, that had partially their transcription to younger cell state, showed local reorganization of inter-chromosomal contacts lamina-associated domains. Interestingly, observed correlated changes. Immunofluorescence experiments state confirmed increased acto-myosin contractility like fibroblasts. In addition, contractile properties were maintained over multiple passages. Overall, our results give an overview how cytoskeleton, chromatin, gene activity connected aging rejuvenation.