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

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.