Spatial Transcriptomics to define transcriptional patterns of zonation and structural components in the liver
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.
Spatial transcriptomics was performed on a total of 8 murine liver tissue sections. The tissue sections were placed in one of six, 6.2 x 6.4 mm frames on the glass slide ST array. Each frame contains 1932 spots, with >200M uniquely barcoded, mRNA capture probes. The distance between centers of each neighboring spot is 150 µm. Initially, each tissue section was fixed, stained with hematoxylin and eosin (H&E), followed by imaging. Tissue sections were permeabilized, followed by mRNA capture, tissue removal and sequencing. Thereafter, the count data was subjected to cluster- and differential gene expression analysis (DGEA).
