Age-related loss of gene-to-gene transcriptional coordination among single cells

Orr Levy, Guy Amit, Dana Vaknin, Tom Snir, Sol Efroni, Peter Castaldi, Yang Yu Liu, Haim Y. Cohen, Amir Bashan

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

A long-standing model holds that stochastic aberrations of transcriptional regulation play a key role in the process of ageing. While transcriptional dysregulation is observed in many cell types in the form of increased cell-to-cell variability, its generality to all cell types remains doubted. Here, we propose a new approach for analysing transcriptional regulation in single-cell RNA sequencing data by focusing on the global coordination between the genes rather than the variability of individual genes or correlations between pairs of genes. Consistently, across very different organisms and cell types, we find a decrease in the gene-to-gene transcriptional coordination in ageing cells. In addition, we find that loss of gene-to-gene transcriptional coordination is associated with high mutational load of a specific, age-related signature and with radiation-induced DNA damage. These observations suggest a general, potentially universal, stochastic attribute of transcriptional dysregulation in ageing.

Original languageEnglish
Pages (from-to)1305-1315
Number of pages11
JournalNature Metabolism
Volume2
Issue number11
DOIs
StatePublished - Nov 2020
Externally publishedYes

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