Single-nucleus RNA-seq2 reveals functional crosstalk between liver zonation and ploidy

M. L. Richter, I. K. Deligiannis, K. Yin, A. Danese, E. Lleshi, P. Coupland, C. A. Vallejos, K. P. Matchett, N. C. Henderson, M. Colome-Tatche () and C. P. Martinez-Jimenez ()
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M. L. Richter: Helmholtz Zentrum München
I. K. Deligiannis: Helmholtz Zentrum München
K. Yin: Helmholtz Zentrum München
A. Danese: Helmholtz Zentrum München
E. Lleshi: University of Cambridge, Cancer Research UK Cambridge Institute, Robinson Way
P. Coupland: University of Cambridge, Cancer Research UK Cambridge Institute, Robinson Way
C. A. Vallejos: University of Edinburgh, Western General Hospital
K. P. Matchett: University of Edinburgh, Little France Crescent
N. C. Henderson: University of Edinburgh, Western General Hospital
M. Colome-Tatche: Helmholtz Zentrum München
C. P. Martinez-Jimenez: Helmholtz Zentrum München

Nature Communications, 2021, vol. 12, issue 1, 1-16

Abstract: Abstract Single-cell RNA-seq reveals the role of pathogenic cell populations in development and progression of chronic diseases. In order to expand our knowledge on cellular heterogeneity, we have developed a single-nucleus RNA-seq2 method tailored for the comprehensive analysis of the nuclear transcriptome from frozen tissues, allowing the dissection of all cell types present in the liver, regardless of cell size or cellular fragility. We use this approach to characterize the transcriptional profile of individual hepatocytes with different levels of ploidy, and have discovered that ploidy states are associated with different metabolic potential, and gene expression in tetraploid mononucleated hepatocytes is conditioned by their position within the hepatic lobule. Our work reveals a remarkable crosstalk between gene dosage and spatial distribution of hepatocytes.

Date: 2021
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DOI: 10.1038/s41467-021-24543-5

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