Integration of transcriptomes of senescent cell models with multi-tissue patient samples reveals reduced COL6A3 as an inducer of senescence

Savić, Radoslav and Yang, Jialiang and Koplev, Simon and An, Mahru C. and Patel, Priyanka L. and O’Brien, Robert N. and Dubose, Brittany N. and Dodatko, Tetyana and Rogatsky, Eduard and Sukhavasi, Katyayani and Ermel, Raili and Ruusalepp, Arno and Houten, Sander M. and Kovacic, Jason C. and Stewart, Andrew F. and Yohn, Christopher B. and Schadt, Eric E. and Laberge, Remi-Martin and Björkegren, Johan L.M. and Tu, Zhidong and Argmann, Carmen (2023) Integration of transcriptomes of senescent cell models with multi-tissue patient samples reveals reduced COL6A3 as an inducer of senescence. Cell Reports, 42 (11). p. 113371. ISSN 22111247

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Link to published document: http://doi.org/10.1016/j.celrep.2023.113371

Abstract

Senescent cells are a major contributor to age-dependent cardiovascular tissue dysfunction, but knowledge of their in vivo cell markers and tissue context is lacking. To reveal tissue-relevant senescence biology, we integrate the transcriptomes of 10 experimental senescence cell models with a 224 multi-tissue gene co-expression network based on RNA-seq data of seven tissues biopsies from approximately 600 coronary artery disease (CAD) patients. We identify 56 senescence-associated modules, many enriched in CAD GWAS genes and correlated with cardiometabolic traits-which supports universality of senescence gene programs across tissues and in CAD. Cross-tissue network analyses reveal 86 candidate senescence-associated secretory phenotype (SASP) factors, including COL6A3. Experimental knockdown of COL6A3 induces transcriptional changes that overlap the majority of the experimental senescence models, with cell-cycle arrest linked to modulation of DREAM complex-targeted genes. We provide a transcriptomic resource for cellular senescence and identify candidate biomarkers, SASP factors, and potential drivers of senescence in human tissues.

Item Type: Article
Subjects: R Medicine > R Medicine (General)
Depositing User: Repository Administrator
Date Deposited: 02 May 2024 06:37
Last Modified: 02 May 2024 06:37
URI: http://eprints.victorchang.edu.au/id/eprint/1495

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