Spatial Transcriptomics to define transcriptional patterns of zonation and structural components in the mouse liver

TLDR

Single‑cell transcriptomics has advanced the understanding of the liver spatial transcriptome, yet global transcriptional differences across lobular units in physical space remain unclear. The authors aim to map liver transcriptional patterns by applying Spatial Transcriptomics to sectioned liver tissue. They performed spatial transcriptomic profiling on liver sections, integrating novel computational approaches to analyze the data. The results reveal that heterogeneity is largely governed by lobular zonation, that computational methods can quantify transcriptional gradients between structures, uncover previously uncharacterized components, and demonstrate that spatial transcriptomics can comprehensively map gene expression patterns with implications for liver function, development, regeneration, and pathology.

Abstract

Abstract Reconstruction of heterogeneity through single cell transcriptional profiling has greatly advanced our understanding of the spatial liver transcriptome in recent years. However, global transcriptional differences across lobular units remain elusive in physical space. Here, we apply Spatial Transcriptomics to perform transcriptomic analysis across sectioned liver tissue. We confirm that the heterogeneity in this complex tissue is predominantly determined by lobular zonation. By introducing novel computational approaches, we enable transcriptional gradient measurements between tissue structures, including several lobules in a variety of orientations. Further, our data suggests the presence of previously transcriptionally uncharacterized structures within liver tissue, contributing to the overall spatial heterogeneity of the organ. This study demonstrates how comprehensive spatial transcriptomic technologies can be used to delineate extensive spatial gene expression patterns in the liver, indicating its future impact for studies of liver function, development and regeneration as well as its potential in pre-clinical and clinical pathology.