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Defining spatiotemporal gene modules in liver regeneration using Analytical Dynamic Visual Spatial Omics

Anya Singh-Varma1,2,3, Ashti M Shah4, Silvia Liu1,2

  • 1Department of Pathology, Division of Experimental Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

Hepatology Communications
|October 27, 2023
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Summary

A new computational tool, ADViSOR, reveals macrophage-mediated inflammation as key to early liver regeneration (LR). It also confirms Wnt/β-catenin pathway regulation of Ccnd1 during LR, offering insights into organ repair.

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Area of Science:

  • Hepatology
  • Computational Biology
  • Systems Biology

Background:

  • The liver's unique capacity for regeneration after injury is modeled by partial hepatectomy.
  • Gene expression patterns change dynamically across liver regions during regeneration.
  • Understanding these spatiotemporal molecular changes is crucial for advancing regenerative medicine.

Purpose of the Study:

  • To investigate the spatiotemporal molecular mechanisms of liver regeneration (LR) using spatial transcriptomics.
  • To introduce and apply a novel computational pipeline, ADViSOR (Analytic Dynamic Visual Spatial Omics Representation), for analyzing complex biological data.
  • To gain insights into the dynamic gene expression and cell signaling during LR.

Main Methods:

  • Spatial transcriptomics was used to analyze gene expression in liver tissue at multiple time points post-partial hepatectomy.
  • The ADViSOR computational pipeline, incorporating Time-Interval Principal Component Analysis and sliding dynamic hypergraphs, was applied to the transcriptomic data.
  • Key components of the Wnt/β-catenin pathway were specifically examined.

Main Results:

  • ADViSOR identified critical functional modules, cell signaling pathways, and cell-cell interactions involved in LR.
  • The analysis highlighted macrophage-mediated inflammation as a significant factor in early-stage LR.
  • It confirmed that Ccnd1, a gene promoting hepatocyte proliferation, is regulated by the Wnt/β-catenin pathway, with findings validated by protein localization studies.

Conclusions:

  • The ADViSOR computational pipeline provides novel insights into the spatiotemporal dynamics of liver regeneration.
  • Macrophage-driven inflammation plays a critical role in the initial phases of liver repair.
  • The study offers a validated computational approach for exploring complex biological processes in other spatiotemporal contexts.