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.
Highlights
The liver is the largest metabolic organ of the human body and vital for blood detoxification and metabolism
We examined the orientation of apical bipolar axes for all hepatocytes within a liver lobule between central vein (CV) and portal vein (PV) (Fig.3A)
While some progress has been made in understanding 2D tissues [13, 15, 24,25,26,27,28,29] such as simple epithelia, the architecture of 3D tissues and its relation to function are poorly understood
Summary
The liver is the largest metabolic organ of the human body and vital for blood detoxification and metabolism. In contrast to simple epithelia, where the cells have a single apical surface facing the lumen of organs, hepatocytes exhibit a multipolar organization, i.e. have multiple apical and basal domains [1, 4, 5] Such organization allows the hepatocytes to have numerous contacts with the sinusoid and BC networks to maximize exchange of substances. Hans Elias in 1949 pioneered the structural analysis of the mammalian liver tissue [6,7,8,9] He proposed a structural model whereby the sinusoids are separated from one another by walls of hepatocytes (one-cell-thick), forming a “continuous system of anastomosing plates, much like the walls separating the rooms within a building” [6, 8]. Analysis of thousands individual hepatocytes revealed the full complexity of distribution of the apical, lateral and basal surfaces
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