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bioRxiv · 10.64898/2026.08.17.745159

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

Wang, Q.·Li, J.·Lyu, Q.
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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 {micro}M 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[&ge;]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.

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Wang, Q., Li, J., Lyu, Q.. 2026-08-19. PCC1 treatment reshapes ribosomal, lysosomal and membrane-lipid transcriptional programs in therapy-induced senescent human stromal cells. https://doi.org/10.64898/2026.08.17.745159

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