Poster Presentation Multi-Omics Conference 2024

Spatial exploration of the maladaptive tissue repair response in chronic liver disease. (#154)

Hani Vu 1 2 , Vera Sun 1 2 , Albert Xiong 1 2 , Andrew Clouston 3 , Katharina Irvine 4 , Elizabeth Powell 2 , Quan Nguyen 1 2
  1. Institute of Molecular Biology, The University of Queensland, Brisbane, Queensland, Australia
  2. QIMR Berghofer, Jindalee, QLD, Australia
  3. Envoi Pathology, Brisbane, Australia
  4. Mater Research Institute, The University of Queensland, Brisbane, Queensland, Australia

The escalating prevenance of metabolic dysfunction-associated steatotic liver disease (MASLD) is a global concern and the development of effective treatments is crucial. Integration of pathological annotations with the spatial transcriptomics data of 33 liver needle biopsies covering a large spectrum of disease severity, from steatosis to cirrhosis, allows histopathologically significant characteristics of the liver to be extracted and analysed. Differential gene analysis specific to each of the 11 histological regions show genes involved in enrichment of ECM component pathways across regions of inflammation and fibrogenesis at advancing stages of fibrosis and PPAR signaling pathway in early-stage fibrosis. Cell type validation using spatial proteomics determined increased presence of Collagen IV and M2 macrophages, promoting ECM deposition with advancing fibrosis. Additionally, high ligand-receptor activity associated with the activation of chemokine signaling pathways and complement and coagulation cascades were highlighted within the inflammatory microenvironment in samples of higher fibrosis severity. This study identifies key molecular mechanisms that underly liver fibrogenesis, translating to potential therapeutic targets to mitigate disease progression.