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.

近年来，通过单细胞转录谱重建异质性极大地促进了我们对空间肝脏转录组的理解。然而，跨小叶单位的全局转录差异在物理空间中仍然难以捉摸。在这里，我们应用空间转录组学对切片的肝组织进行转录组学分析。我们确认这种复杂组织的异质性主要由小叶分区决定。通过引入新的计算方法，我们可以在组织结构之间进行转录梯度测量，包括多个方向不同的小叶。此外，我们的数据表明，肝组织内存在以前转录未表征的结构，导致器官的整体空间异质性。