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

Author

Listed:
  • M. L. Richter

    (Helmholtz Zentrum München)

  • I. K. Deligiannis

    (Helmholtz Zentrum München)

  • K. Yin

    (Helmholtz Zentrum München
    University of Cambridge, Cancer Research UK Cambridge Institute, Robinson Way)

  • 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
    University of Edinburgh, Little France Crescent)

  • M. Colome-Tatche

    (Helmholtz Zentrum München
    TUM School of Life Sciences Weihenstephan, Technical University of Munich
    LMU Munich)

  • C. P. Martinez-Jimenez

    (Helmholtz Zentrum München
    TUM School of Medicine, Technical University of Munich)

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.

Suggested Citation

  • 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 & C. P. Martinez-Jimenez, 2021. "Single-nucleus RNA-seq2 reveals functional crosstalk between liver zonation and ploidy," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24543-5
    DOI: 10.1038/s41467-021-24543-5
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    References listed on IDEAS

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    1. Bruce Wang & Ludan Zhao & Matt Fish & Catriona Y. Logan & Roel Nusse, 2015. "Self-renewing diploid Axin2+ cells fuel homeostatic renewal of the liver," Nature, Nature, vol. 524(7564), pages 180-185, August.
    2. Xianghua Li & Jasna Lalić & Pablo Baeza-Centurion & Riddhiman Dhar & Ben Lehner, 2019. "Changes in gene expression predictably shift and switch genetic interactions," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
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    Cited by:

    1. Marko Dunjić & Felix Jonas & Gilad Yaakov & Roye More & Yoav Mayshar & Yoach Rais & Ayelet-Hashahar Orenbuch & Saifeng Cheng & Naama Barkai & Yonatan Stelzer, 2023. "Histone exchange sensors reveal variant specific dynamics in mouse embryonic stem cells," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    2. Johanna Beil & Juliane Perner & Lena Pfaller & Marie-Apolline Gérard & Alessandro Piaia & Arno Doelemeyer & Adi Wasserkrug Naor & Lori Martin & Aline Piequet & Valérie Dubost & Salah-Dine Chibout & Jo, 2023. "Unaltered hepatic wound healing response in male rats with ancestral liver injury," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

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