Z Gastroenterol 2019; 57(01): e10
DOI: 10.1055/s-0038-1677063
1. Basic Hepatology (Fibrogenesis, NPC, Transport)
Georg Thieme Verlag KG Stuttgart · New York

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

M Brosch
1   Medical Department 1, University Hospital Dresden, Technische Universität Dresden (TU Dresden), Dresden, Germany
,
K Kattler
2   Department of Genetics and Epigenetics, Universität des Saarlandes, Saarbrücken, Germany
,
A Herrmann
1   Medical Department 1, University Hospital Dresden, Technische Universität Dresden (TU Dresden), Dresden, Germany
,
W von Schönfels
3   Department of Visceral Surgery, University Hospital Schleswig-Holstein, Christian-Albrechts-University Kiel, Kiel, Germany
,
K Nordström
2   Department of Genetics and Epigenetics, Universität des Saarlandes, Saarbrücken, Germany
,
D Seehofer
4   Department of Hepatobiliary Surgery and Visceral Transplantation, University of Leipzig, Leipzig, Germany
,
G Damm
4   Department of Hepatobiliary Surgery and Visceral Transplantation, University of Leipzig, Leipzig, Germany
,
T Becker
3   Department of Visceral Surgery, University Hospital Schleswig-Holstein, Christian-Albrechts-University Kiel, Kiel, Germany
,
S Zeissig
1   Medical Department 1, University Hospital Dresden, Technische Universität Dresden (TU Dresden), Dresden, Germany
,
S Nehring
1   Medical Department 1, University Hospital Dresden, Technische Universität Dresden (TU Dresden), Dresden, Germany
,
F Reichel
1   Medical Department 1, University Hospital Dresden, Technische Universität Dresden (TU Dresden), Dresden, Germany
,
V Moser
1   Medical Department 1, University Hospital Dresden, Technische Universität Dresden (TU Dresden), Dresden, Germany
,
RV Thangapandi
1   Medical Department 1, University Hospital Dresden, Technische Universität Dresden (TU Dresden), Dresden, Germany
,
F Stickel
5   Department of Gastroenterology, University of Zürich, Zürich, Switzerland
,
G Baretton
6   Institute of Pathology, University Hospital Dresden, Technische Universität Dresden (TU Dresden), Dresden, Germany
,
C Röcken
7   Institute of Pathology, University Hospital Schleswig-Holstein, Christian-Albrechts-University Kiel, Kiel, Germany
,
M Muders
6   Institute of Pathology, University Hospital Dresden, Technische Universität Dresden (TU Dresden), Dresden, Germany
,
M Matz-Soja
8   Rudolf-Schönheimer-Institute for Biochemistry, University of Leipzig, Leipzig, Germany.
,
M Krawczak
9   Institute of Medical Informatics and Statistics, Christian-Albrechts University, Kiel, Germany.
,
G Gasparoni
2   Department of Genetics and Epigenetics, Universität des Saarlandes, Saarbrücken, Germany
,
H Hartmann
10   Center for Molecular and Cellular Bioengineering (CMCB), Technische Universität Dresden (TU Dresden), Dresden, Germany
,
A Dahl
11   Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden (TU Dresden), Dresden, Germany
,
C Schafmayer
3   Department of Visceral Surgery, University Hospital Schleswig-Holstein, Christian-Albrechts-University Kiel, Kiel, Germany
,
J Walter
2   Department of Genetics and Epigenetics, Universität des Saarlandes, Saarbrücken, Germany
,
J Hampe
1   Medical Department 1, University Hospital Dresden, Technische Universität Dresden (TU Dresden), Dresden, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
04 January 2019 (online)

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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.