1. Inter-tissue convergence of gene expression during ageing suggests age-related loss of tissue and cellular identity
- Author
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Hamit Izgi, Dingding Han, Ulas Isildak, Shuyun Huang, Ece Kocabiyik, Philipp Khaitovich, Mehmet Somel, and Handan Melike Dönertaş
- Subjects
ageing ,development ,transcriptome ,mouse ,reversal ,Medicine ,Science ,Biology (General) ,QH301-705.5 - Abstract
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 (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.
- Published
- 2022
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