Liquid-crystal organization of liver tissue
- Max Planck Institute for Cell Biology and Genetics, Germany
- Max Planck Institute for the Physics of Complex Systems, Germany
- Technische Universität Dresden, Germany
- Massachusetts Institute of Technology, United States
- Skolkovo Institute of Science and Technology, Russian Federation
Abstract
Functional tissue architecture originates by self-assembly of distinct cell types, following tissue-specific rules of cell-cell interactions. In the liver, a structural model of the lobule was pioneered by Elias in 1949. This model, however, is in contrast with the apparent random 3D arrangement of hepatocytes. Since then, no significant progress has been made to derive the organizing principles of liver tissue. To solve this outstanding problem, we computationally reconstructed 3D tissue geometry from microscopy images of mouse liver tissue and analyzed it applying soft-condensed-matter-physics concepts. Surprisingly, analysis of the spatial organization of cell polarity revealed that hepatocytes are not randomly oriented but follow a long-range liquid-crystal order. This does not depend exclusively on hepatocytes receiving instructive signals by endothelial cells, since silencing Integrin-β1 disrupted both liquid-crystal order and organization of the sinusoidal network. Our results suggest that bi-directional communication between hepatocytes and sinusoids underlies the self-organization of liver tissue.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Figure 1-figure supplement 2 and Figure 1-figure supplement 3
Article and author information
Author details
Hernán Morales-Navarrete
Fabián Segovia-Miranda
Benjamin M Friedrich
Funding
H2020 European Research Council (Grant number 695646)
- Hernán Morales-Navarrete
Bundesministerium für Bildung und Forschung (LiSyM-031L0038)
- Fabián Segovia-Miranda
- Kirstin Meyer
Deutsche Forschungsgemeinschaft (Cluster of Excellence EXC 1056 cfaed)
- Benjamin M Friedrich
Max-Planck-Gesellschaft (Open-access funding)
- Hidenori Nonaka
Bundesministerium für Bildung und Forschung (SYSBIO II-031L0044)
- Fabián Segovia-Miranda
- Kirstin Meyer
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Pierre Sens, Institut Curie, PSL Research University, CNRS, France
Ethics
Animal experimentation: All procedures were performed in compliance with German animal welfarelegislation and in pathogen-free conditions in the animal facility ofthe MPI-CBG, Dresden, Germany. Protocols were approved by theInstitutional Animal Welfare Officer (Tierschutzbeauftragter) and allnecessary licenses were obtained from the regional Ethical Commissionfor Animal Experimentation of Dresden, Germany (Tierversuchskommission,Landesdirektion Dresden)(License number: DD24-5131/338/50).
Version history
- Received: January 4, 2019
- Accepted: June 14, 2019
- Accepted Manuscript published: June 17, 2019 (version 1)
- Version of Record published: June 28, 2019 (version 2)
Copyright
© 2019, Morales-Navarrete et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Liquid-crystal organization of liver tissue
eLife 8:e44860.
https://doi.org/10.7554/eLife.44860
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