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PCC1 treatment reshapes ribosomal, lysosomal and membrane-lipid transcriptional programs in therapy-induced senescent human stromal cells

Created on 19 Aug 2026

Authors

Wang, Q., Li, J., Lyu, Q.

Abstract

Cellular senescence combines stable proliferative arrest with extensive changes in secretory, metabolic and organelle programs. Procyanidin C1 (PCC1) has dose-dependent senomorphic and senolytic activity, but the structure of its transcriptome-wide response is not well defined. We reanalyzed published RNA-sequencing counts from bleomycin-induced senescent PSC27 human stromal cells treated with 50 uM PCC1. The primary contrast contained three independent biological replicates per condition. PCC1 altered 8,420 genes at adjusted P<0.05 and absolute log2 fold change[≥]1. Ribosomal genes showed the clearest coordinated response, followed by lysosomal genes. Analysis across the full ontologies also identified lysosomal-membrane, proton-transport,late-endosome, lipid-localization, cholesterol and fatty-acid programs. Prespecified analyses revealed two trajectories relative to senescence. Lipid-transport, lipid-binding and plasma-membrane programs decreased during senescence and increased after PCC1, whereas lysosomal-membrane, mitochondrial-membrane, cholesterol and ion-transport programs increased in both contrasts. Senescence-associated outputs were more selective. A prespecified SASP-effector score decreased, but a broad Reactome SASP set did not pass false-discovery correction. AP-1-family expression shifted, and an HSP90/HSF1/proteostasis panel increased. Together, these data support a model in which PCC1 induces coordinated transcriptomic remodeling in senescent stromal cells, encompassing membrane-lipid remodeling, changes in cellular infrastructure, and selective modulation of senescence-associated outputs.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 19 Aug 2026.

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