INTER-TISSUE CONVERGENCE OF GENE EXPRESSION AND LOSS OF IDENTITY DURING AGEING

Date

2023-9-04

Author

İzgi, Hamit

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Gene expression trajectories during development tend to reverse their direction in ageing, a phenomenon previously reported in primate brain tissues. This reversal phenomenon was linked to cellular identity loss during ageing. Motivated by this observation, we studied the prevalence of reversals in different mouse tissues. Gen- erating transcriptome data from cortex, lung, liver and muscle tissues of 16 mice, covering both development and ageing intervals, we fould widespread but tissue spe- cific ageing-associated expression reversals. Cumulatively, these reversals create a unique phenomenon: mammalian tissue transcriptomes diverge from each other dur- ing postnatal development, but during ageing, they tend to converge towards similar expression levels, a process we term divergence-convergence, or DiCo. We revealed that genes showing DiCo pattern are associated with tissue-specific genes, a possible indication of loss of tissue-specificy during ageing. We found further evidence for the DiCo pattern using data from independent mouse and human datasets. Moreover, 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, Transcriptome, Mouse model, loss of identity

URI

https://hdl.handle.net/11511/105514

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Graduate School of Natural and Applied Sciences, Thesis