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

• Published in: Nature communications Vol. 12; no. 1; p. 7046
• Main Authors: Hildebrandt, Franziska, Andersson, Alma, Saarenpää, Sami, Larsson, Ludvig, Van Hul, Noémi, Kanatani, Sachie, Masek, Jan, Ellis, Ewa, Barragan, Antonio, Mollbrink, Annelie, Andersson, Emma R., Lundeberg, Joakim, Ankarklev, Johan
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 02.12.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 38; 38/91; 45; 631/1647/2217/2218; 631/208/514/1949; 631/61/212/2019; 692/4020/4021/288/2032; Animals; B-Lymphocytes - cytology; B-Lymphocytes - metabolism; Computer applications; Dendritic Cells - cytology; Dendritic Cells - metabolism; Endothelial Cells - cytology; Endothelial Cells - metabolism; Erythroblasts - cytology; Erythroblasts - metabolism; Female; Gene expression; Gene Expression Profiling; Gene Ontology; Genetic Heterogeneity; Hepatocytes - cytology; Hepatocytes - metabolism; Heterogeneity; Humanities and Social Sciences; Kupffer Cells - cytology; Kupffer Cells - metabolism; Liver; Liver - cytology; Liver - metabolism; Macrophages - cytology; Macrophages - metabolism; Medicin och hälsovetenskap; Mice; Mice, Inbred C57BL; Molecular Sequence Annotation; multidisciplinary; Neutrophils - cytology; Neutrophils - metabolism; Regeneration; Science; Science (multidisciplinary); Spatial heterogeneity; Tissues; Transcription; Transcriptome; Transcriptomes; Transcriptomics; Zonation
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-27354-w

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. Global transcriptional differences across lobular units in the liver remain unknown. Here the authors perform spatial transcriptomics of liver tissue to delineate transcriptional differences in physical space, confirm lobular zonation along transcriptional gradients and suggest the presence of previously uncharacterized structures within liver tissue.