Proliferative stress in hematopoietic stem cells partially drives their functional decline during aging by DNA methylation imprints
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ABSTRACT:
PROVIDER: PRJNA1146326 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR30184200.fastq.gz | Fastqsanger.gz | |||
| SRR30184201.fastq.gz | Fastqsanger.gz | |||
| SRR30184202.fastq.gz | Fastqsanger.gz | |||
| SRR30184203.fastq.gz | Fastqsanger.gz | |||
| SRR30184204.fastq.gz | Fastqsanger.gz |
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Project description:Aging of the vasculature is associated with detrimental changes in vascular smooth muscle cell (VSMC) mechanosensitivity to extrinsic forces in their surrounding microenvironment. However, how chronological aging alters VSMCs’ ability to sense and adapt to mechanical perturbations remains unexplored. Here, we show defective VSMC mechanosensation in aging measured with ultrasound tweezers-based micromechanical system, force instantaneous frequency spectrum and transcriptome analyses. The mechanobiological study reveals thataged VSMCs adapt a relatively inert solid-like state with altered actin cytoskeletal integrity, resulting in an impairment in their mechanosensitivity and dynamic mechanoresponse to mechanical perturbations. The aging-associated decline in mechanosensation behaviors is mediated by hyperactivity of Piezo1-dependent calcium signaling. Inhibition of Piezo1 alleviates vascular aging and partially restores the loss in dynamic contractile properties in aged cells. Altogether, our study reveals the novel signaling pathway underlying aging-associated aberrant mechanosensation in VSMC and identifies Piezo1 as a potential therapeutic mechanobiological target to alleviate vascular aging.
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