Multiple time-series expression trajectories imply dynamic functional changes during cellular senescence

Cellular senescence is a dynamic process driven by epigenetic and genetic changes. Although some tran-scriptomic signatures of senescent cells have been discovered, how these senescence-related signals change over time remains largely unclear. Here, we profiled the transcriptome dynamics of human der-mal fibroblast (HDF) cells in successive stages of growth from proliferation to senescence. Based on time -series expression profile analysis, we discovered four trajectories (C1, C2, C3, C4) that are dynamically expressed as senescence progresses. While some genes were continuously up-regulated (C4) or down -regulated (C2) with aging, other genes did not change linearly with cell proliferation, but remained stable until entering the senescent state (C1, C3). Further analysis revealed that the four modes were enriched in different biological pathways, including regulation of cellular senescence. These findings provide a new perspective on understanding the dynamic regulatory mechanism of cellular senescence. (c) 2022 The Authors. Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology. This is an open access article under the CC BY-NC-ND license (http://creative-commons.org/licenses/by-nc-nd/4.0/).

Automated summary

This study profiles the transcriptome dynamics of human dermal fibroblast cells during the progression from proliferation to senescence. Four trajectories of gene expression changes were identified as senescence progresses. Some genes showed continuous up-regulation or down-regulation, while others remained stable until entering the senescent state. These findings provide new insights into the dynamic regulatory mechanism of cellular senescence.