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

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2022-01-01

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İzgi, Hamit
Han, Dingding
Isildak, Ulas
Huang, Shuyun
Kocabiyik, Ece
Khaitovich, Philipp
Somel, Mehmet
Dönertaş, Handan Melike

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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.

Subject Keywords

Ageing, Development, Mouse, Reversal, Transcriptome

URI

https://hdl.handle.net/11511/96666

Journal

eLife

DOI

https://doi.org/10.7554/elife.68048

Collections

Department of Biology, Article

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Citation Formats

H. İzgi et al., “Inter-tissue convergence of gene expression during ageing suggests age-related loss of tissue and cellular identity,” eLife, vol. 11, pp. 0–0, 2022, Accessed: 00, 2022. [Online]. Available: https://hdl.handle.net/11511/96666.