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

Ming-Xia Ge; Qin Yu; Gong-Hua Li; Li-Qin Yang; Yonghan He; Ji Li; Qing-Peng Kong

doi:10.1016/j.csbj.2022.08.005

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

Comput Struct Biotechnol J. 2022 Aug 5:20:4131-4137. doi: 10.1016/j.csbj.2022.08.005. eCollection 2022.

Authors

Ming-Xia Ge^{1

2

3

4

5}, Qin Yu¹, Gong-Hua Li¹, Li-Qin Yang¹, Yonghan He¹, Ji Li^{6

7

8}, Qing-Peng Kong^{1

2

3

4}

Affiliations

¹ 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.
² CAS Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming, Yunnan 650201, China.
³ Kunming Key Laboratory of Healthy Aging Study, Kunming, Yunnan 650201, China.
⁴ KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming, Yunnan 650201, China.
⁵ Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing 100049, China.
⁶ Department of Dermatology/National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410000, China.
⁷ Hunan Key Laboratory of Aging Biology, Xiangya Hospital, Central South University, Changsha 410000, China.
⁸ Department of Dermatology, Second Affiliated Hospital of Xinjiang Medical University, Urumqi 830000, China.

Abstract

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.

Keywords: Cellular senescence; Expression profile; Time-series analysis; Trajectory; Transcriptome.