Inter-tissue convergence of gene expression during ageing suggests age-related loss of tissue and cellular identity

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İZGİ H., Han D., Isildak U., Huang S., Kocabiyik E., Khaitovich P., ...More

eLife, vol.11, 2022 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 11
  • Publication Date: 2022
  • Doi Number: 10.7554/elife.68048
  • Journal Name: eLife
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, EMBASE, MEDLINE, Veterinary Science Database, Directory of Open Access Journals
  • Keywords: ageing, development, transcriptome, mouse, reversal, Human, Mouse, RNA, TRANSFAC(R), VARIABILITY, PACKAGE
  • Middle East Technical University Affiliated: Yes


© 2022, eLife Sciences Publications Ltd. All rights reserved.(124/150 words) Developmental trajectories of gene expression may reverse in their direction during ageing, a phenomenon previously linked to cellular identity loss. Our analysis of cerebral cortex, lung, liver and muscle transcriptomes of 16 mice, covering development and ageing intervals, revealed widespread but tissue-specific ageing-associated expression reversals. Cumulatively, these reversals create a unique phenomenon: mammalian tissue transcriptomes diverge from each other during postnatal development, but during ageing, they tend to converge towards similar expression levels, a process we term Divergence followed by Convergence, or DiCo. We found that DiCo was most prevalent among tissue-specific genes and associated with loss of tissue identity, which is confirmed using data from independent mouse and human datasets. Further, using publicly available single-cell transcriptome data, we showed that DiCo could be driven both by alterations in tissue cell type composition and also by cell-autonomous expression changes within particular cell types.