Geometric and network organization of visceral organ epithelium

Betty S Liu; Joseph Sutlive; Willi L Wagner; Hassan A Khalil; Zi Chen; Maximilian Ackermann; Steven J Mentzer

doi:10.3389/fnetp.2023.1144186

Geometric and network organization of visceral organ epithelium

Front Netw Physiol. 2023 May 10:3:1144186. doi: 10.3389/fnetp.2023.1144186. eCollection 2023.

Authors

Betty S Liu¹, Joseph Sutlive¹, Willi L Wagner², Hassan A Khalil¹, Zi Chen¹, Maximilian Ackermann³, Steven J Mentzer¹

Affiliations

¹ Laboratory of Adaptive and Regenerative Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.
² Translational Lung Research Center, Department of Diagnostic and Interventional Radiology, University of Heidelberg, Heidelberg, Germany.
³ Institute of Functional and Clinical Anatomy, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.

Abstract

Mammalian epithelia form a continuous sheet of cells that line the surface of visceral organs. To analyze the epithelial organization of the heart, lung, liver and bowel, epithelial cells were labeled in situ, isolated as a single layer and imaged as large epithelial digitally combine montages. The stitched epithelial images were analyzed for geometric and network organization. Geometric analysis demonstrated a similar polygon distribution in all organs with the greatest variability in the heart epithelia. Notably, the normal liver and inflated lung demonstrated the largest average cell surface area (p < 0.01). In lung epithelia, characteristic wavy or interdigitated cell boundaries were observed. The prevalence of interdigitations increased with lung inflation. To complement the geometric analyses, the epithelia were converted into a network of cell-to-cell contacts. Using the open-source software EpiGraph, subgraph (graphlet) frequencies were used to characterize epithelial organization and compare to mathematical (Epi-Hexagon), random (Epi-Random) and natural (Epi-Voronoi5) patterns. As expected, the patterns of the lung epithelia were independent of lung volume. In contrast, liver epithelia demonstrated a pattern distinct from lung, heart and bowel epithelia (p < 0.05). We conclude that geometric and network analyses can be useful tools in characterizing fundamental differences in mammalian tissue topology and epithelial organization.

Keywords: cell size; connectivity (graph theory); epithelial cells; pleura; visceral organ.