TY - JOUR TI - Inter-tissue convergence of gene expression during ageing suggests age-related loss of tissue and cellular identity AU - Izgi, Hamit AU - Han, Dingding AU - Isildak, Ulas AU - Huang, Shuyun AU - Kocabiyik, Ece AU - Khaitovich, Philipp AU - Somel, Mehmet AU - Dönertaş, Handan Melike A2 - Benayoun, Bérénice A A2 - Cheah, Kathryn Song Eng VL - 11 PY - 2022 DA - 2022/01/31 SP - e68048 C1 - eLife 2022;11:e68048 DO - 10.7554/eLife.68048 UR - https://doi.org/10.7554/eLife.68048 AB - 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. KW - ageing KW - development KW - transcriptome KW - mouse KW - reversal JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -