(2/n) Studying gene expression trajectories, we found that developmental trajectories don't necessarily continue into ageing (gene expression trajectories show reversal). but, reversals were not shared across tissues 🤨
(3/n) We, then, hypothesised that reversals may contribute to tissue divergence during development while they are gaining a "tissue identity" but convergence during ageing as they lose their tissue-specific expression signatures 🤔
(4/n) Indeed, we find a strong inter-tissue divergence during development, followed by a weak transcriptome-wide convergence in ageing. We also show tissue-specific genes lose their expression or non-native tissues start to express non-specific genes, contributing to DiCo.
(5/n) Transcriptome-wide signal for inter-tissue convergence is weak but observed at different levels, in multiple datasets and most importantly, the signal for tissue identity loss for DiCo genes is strong across datasets, different sets of tissues and in mice and humans.
(6/n) Using external scRNA-seq data, we conclude not only changes in cell-type proportions but cell-autonomous changes may also contribute to the DiCo pattern. All these support the notion of loss of tissue (and maybe cellular) identity with ageing.
(7/n) It was a privilege to work with amazing colleagues from @CompEvoMetu and Khaitovich Labs! And thanks a million to @hmtzgi for putting this huge effort together and especially persevering with the revisions during the peak time of covid19!!
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