Department of Molecular Biosciences, the Wenner-Gren Institute, Stockholm University, Svante Arrhenius Väg 20C, SE-106 91, Stockholm, Sweden.
Science for Life Laboratory, Department of Gene Technology, KTH Royal Institute of Technology, Tomtebodavägen 23a, SE-171 65, Solna, Sweden.
Nat Commun. 2021 Dec 2;12(1):7046. 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.
近年来，通过单细胞转录组分析进行异质性重建极大地提高了我们对肝脏空间转录组的理解。然而，在物理空间中，肝小叶单元之间的整体转录差异仍然难以捉摸。在这里，我们应用空间转录组学对切片肝组织进行转录组分析。我们证实，这种复杂组织的异质性主要由小叶区带决定。通过引入新的计算方法，我们能够在组织结构之间进行转录梯度测量，包括各种方向的多个小叶。此外，我们的数据表明，肝组织内存在以前未被转录特征化的结构，这有助于器官的整体空间异质性。这项研究表明，全面的空间转录组学技术如何用于描绘肝脏中广泛的空间基因表达模式，这表明它在未来对肝脏功能、发育和再生的研究以及在临床前和临床病理学中的潜在应用方面具有重要意义。
