Single-cell RNA-sequencing reveals widespread personalized, context-specific gene expression regulation in immune cells.

Oelen, R.; de Vries, D. H.; Brugge, H.; Gordon, G.; Vochteloo, M.; Ye, C. J.; Westra, H.-J.; Franke, L.; van der Wijst, M. G. P.

doi:10.1101/2021.06.04.447088

bioRxiv · 10.1101/2021.06.04.447088

Single-cell RNA-sequencing reveals widespread personalized, context-specific gene expression regulation in immune cells.

Oelen, R.·de Vries, D. H.·Brugge, H.·Gordon, G.·Vochteloo, M.·Ye, C. J.·Westra, H.-J.·Franke, L.·van der Wijst, M. G. P.

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Abstract

Gene expression and its regulation can be context-dependent. To dissect this, using samples from 120 individuals, we single-cell RNA-sequenced 1.3M peripheral blood mononuclear cells exposed to three different pathogens at two time points or left unexposed. This revealed thousands of cell type-specific expression changes (eQTLs) and pathogen-induced expression changes (response QTLs) that are influenced by genetic variation. In monocytes, the strongest responder to pathogen stimulations, genetics also affected co-expression of 71.4% of these eQTL genes. For example, the pathogen recognition receptor CLEC12A showed many such co-expression interactions, but only in monocytes after 3h pathogen stimulation. Further analysis linked this to interferon-regulating transcription factors, a finding that we recapitulated in an independent cohort of patients with systemic lupus erythematosus, a condition characterized by increased interferon activity. Altogether, this study highlights the importance of context for gaining a better understanding of the mechanisms of gene regulation in health and disease.

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Oelen, R., de Vries, D. H., Brugge, H., Gordon, G., Vochteloo, M., Ye, C. J., Westra, H.-J., Franke, L., van der Wijst, M. G. P.. 2021-06-06. Single-cell RNA-sequencing reveals widespread personalized, context-specific gene expression regulation in immune cells.. https://doi.org/10.1101/2021.06.04.447088

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