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Epigenomic map of human liver reveals principles of zonated morphogenic and metabolic control

Author

Listed:
  • Mario Brosch

    (Technische Universität Dresden (TU Dresden)
    Technische Universität Dresden (TU Dresden))

  • Kathrin Kattler

    (Universität des Saarlandes)

  • Alexander Herrmann

    (Technische Universität Dresden (TU Dresden)
    Technische Universität Dresden (TU Dresden))

  • Witigo von Schönfels

    (Christian-Albrechts-University Kiel)

  • Karl Nordström

    (Universität des Saarlandes)

  • Daniel Seehofer

    (University of Leipzig)

  • Georg Damm

    (University of Leipzig)

  • Thomas Becker

    (Christian-Albrechts-University Kiel)

  • Sebastian Zeissig

    (Technische Universität Dresden (TU Dresden))

  • Sophie Nehring

    (Technische Universität Dresden (TU Dresden))

  • Fabian Reichel

    (Technische Universität Dresden (TU Dresden))

  • Vincent Moser

    (Technische Universität Dresden (TU Dresden))

  • Raghavan Veera Thangapandi

    (Technische Universität Dresden (TU Dresden))

  • Felix Stickel

    (University of Zürich)

  • Gustavo Baretton

    (Technische Universität Dresden (TU Dresden))

  • Christoph Röcken

    (Christian-Albrechts-University Kiel)

  • Michael Muders

    (Technische Universität Dresden (TU Dresden))

  • Madlen Matz-Soja

    (University of Leipzig)

  • Michael Krawczak

    (Christian-Albrechts University)

  • Gilles Gasparoni

    (Universität des Saarlandes)

  • Hella Hartmann

    (Technische Universität Dresden (TU Dresden))

  • Andreas Dahl

    (Technische Universität Dresden (TU Dresden))

  • Clemens Schafmayer

    (Christian-Albrechts-University Kiel)

  • Jörn Walter

    (Universität des Saarlandes)

  • Jochen Hampe

    (Technische Universität Dresden (TU Dresden)
    Technische Universität Dresden (TU Dresden))

Abstract

A deeper epigenomic understanding of spatial organization of cells in human tissues is an important challenge. Here we report the first combined positional analysis of transcriptomes and methylomes across three micro-dissected zones (pericentral, intermediate and periportal) of human liver. We identify pronounced anti-correlated transcriptional and methylation gradients including a core of 271 genes controlling zonated metabolic and morphogen networks and observe a prominent porto-central gradient of DNA methylation at binding sites of 46 transcription factors. The gradient includes an epigenetic and transcriptional Wnt signature supporting the concept of a pericentral hepatocyte regeneration pathway under steady-state conditions. While donors with non-alcoholic fatty liver disease show consistent gene expression differences corresponding to the severity of the disease across all zones, the relative zonated gene expression and DNA methylation patterns remain unchanged. Overall our data provide a wealth of new positional insights into zonal networks controlled by epigenetic and transcriptional gradients in human liver.

Suggested Citation

  • Mario Brosch & Kathrin Kattler & Alexander Herrmann & Witigo von Schönfels & Karl Nordström & Daniel Seehofer & Georg Damm & Thomas Becker & Sebastian Zeissig & Sophie Nehring & Fabian Reichel & Vince, 2018. "Epigenomic map of human liver reveals principles of zonated morphogenic and metabolic control," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06611-5
    DOI: 10.1038/s41467-018-06611-5
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    Cited by:

    1. Sun Woo Sophie Kang & Rory P. Cunningham & Colin B. Miller & Lauryn A. Brown & Constance M. Cultraro & Adam Harned & Kedar Narayan & Jonathan Hernandez & Lisa M. Jenkins & Alexei Lobanov & Maggie Cam , 2024. "A spatial map of hepatic mitochondria uncovers functional heterogeneity shaped by nutrient-sensing signaling," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    2. Sen Qiao & Samer Alasmi & Amanda Wyatt & Philipp Wartenberg & Hongmei Wang & Michael Candlish & Debajyoti Das & Mari Aoki & Ramona Grünewald & Ziyue Zhou & Qinghai Tian & Qiang Yu & Viktoria Götz & An, 2023. "Intra-pituitary follicle-stimulating hormone signaling regulates hepatic lipid metabolism in mice," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    3. David Requena & Jack A. Medico & Luis F. Soto-Ugaldi & Mahsa Shirani & James A. Saltsman & Michael S. Torbenson & Philip Coffino & Sanford M. Simon, 2024. "Liver cancer multiomics reveals diverse protein kinase A disruptions convergently produce fibrolamellar hepatocellular carcinoma," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    4. Agnieska Brazovskaja & Tomás Gomes & Rene Holtackers & Philipp Wahle & Christiane Körner & Zhisong He & Theresa Schaffer & Julian Connor Eckel & René Hänsel & Malgorzata Santel & Makiko Seimiya & Timm, 2024. "Cell atlas of the regenerating human liver after portal vein embolization," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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