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Transcription-Associated Chromatin Reorganization During Cellular Rejuvenation (Hi-C)

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 proposed. However, the epigenetic mechanisms underlying cellular rejuvenation are poorly understood. We studied the transcriptional and genome-wide chromatin organization changes in young, aged and mechanically rejuvenated fibroblasts using RNA-seq and Hi-C experiments. The mechanically rejuvenated aged fibroblasts, that had reset their transcription to a younger cell state, showed a reorganization of the inter-chromosomal contacts and lamina-associated domains. Interestingly, the observed chromatin reorganization correlated with the transcriptional changes. Immunofluorescence experiments in the rejuvenated state confirmed increased contractility and reduced chromosome copy number variations, similar to younger fibroblasts. In addition, the rejuvenated contractile properties were maintained over multiple cell passages. Taken together, our results provide a multi-scale characterization of the chromatin reorganization that accompanies cellular aging and rejuvenation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE237268 | GEO | 2024/03/20

REPOSITORIES: GEO

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Transcription-Associated Chromatin Reorganization During Cellular Rejuvenation (RNA-Seq)

Project description:Aging is associated with a progressive decline in cellular function. To reset the aged cellular phenotype, various reprogramming approaches, including mechanical routes, have been proposed. However, the epigenetic mechanisms underlying cellular rejuvenation are poorly understood. We studied the transcriptional changes in young, aged and mechanically rejuvenated fibroblasts using RNA-seq. The mechanically rejuvenated aged fibroblasts, that had reset their transcription to a younger cell state. In addition, the rejuvenated cells contractile properties were maintained over multiple cell passages. Taken together, our results provide a multi-scale characterization of the chromatin reorganization that accompanies cellular aging and rejuvenation.

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