LiverMap pipeline for 3D imaging of human liver reveals volumetric spatial dysregulation of cirrhotic vasculobiliary architecture.

Autor: Fabyan WB, Fortin CL, Kenerson HL, Simmonds SP, Liu JTC, Yeh MM, Carr RM, Yeung RSW, Stevens KR
Jazyk: angličtina
Zdroj: BioRxiv : the preprint server for biology [bioRxiv] 2024 Sep 19. Date of Electronic Publication: 2024 Sep 19.
DOI: 10.1101/2024.09.14.613049
Abstrakt: The liver contains an intricate microstructure that is critical for liver function. Architectural disruption of this spatial structure is pathologic. Unfortunately, 2D histopathology - the gold standard for pathological understanding of many liver diseases - can misrepresent or leave gaps in our understanding of complex 3D structural features. Here, we utilized immunostaining, tissue clearing, microscopy, and computational software to create 3D multilobular reconstructions of both non-fibrotic and cirrhotic human liver tissue. We found that spatial architecture in human cirrhotic liver samples with varying etiologies had sinusoid zonation dysregulation, reduction in glutamine synthetase-expressing pericentral hepatocytes, regression of central vein networks, disruption of hepatic arterial networks, and fragmentation of biliary networks, which together suggest a pro-portalization/decentralization phenotype in cirrhotic tissue. Further implementation of 3D pathological analyses may provide a deeper understanding of cirrhotic pathobiology and inspire novel treatments for liver disease.
Databáze: MEDLINE