Ge Ming-Xia, Yu Qin, Li Gong-Hua, Yang Li-Qin, He Yonghan, Li Ji, Kong Qing-Peng
State Key Laboratory of Genetic Resources and Evolution/Key Laboratory of Healthy Aging Research of Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650201, China.
CAS Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming, Yunnan 650201, China.
Comput Struct Biotechnol J. 2022 Aug 5;20:4131-4137. doi: 10.1016/j.csbj.2022.08.005. eCollection 2022.
Cellular senescence is a dynamic process driven by epigenetic and genetic changes. Although some transcriptomic 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 dermal 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.
细胞衰老 是一个由表观遗传和基因变化驱动的动态过程。尽管已经发现了衰老细胞的一些转录组特征,但这些衰老相关信号如何随时间变化在很大程度上仍不清楚。在这里,我们描绘了人类皮肤成纤维细胞(HDF)从增殖到衰老的连续生长阶段的转录组动态变化。基于时间序列表达谱分析,我们发现了四条随着衰老进程动态表达的轨迹(C1、C2、C3、C4)。虽然一些基因随着衰老持续上调(C4)或下调(C2),但其他基因并不随细胞增殖呈线性变化,而是在进入衰老状态之前保持稳定(C1、C3)。进一步分析表明,这四种模式在不同的生物学途径中富集,包括细胞衰老的调控。这些发现为理解细胞衰老的动态调控机制提供了新的视角。