STOmics technology:BGI Stereomics Stereo-Seq

Data type:Spatial transcriptomics

Sample scope:Monoisolate

Summary:The gut-liver axis is a complex bidirectional communication pathway between the intestine and the liver in which microorganisms and their metabolites from the intestine flow through the portal vein to the liver and influence liver function. In a sterile environment, the phenotype or function of the liver is altered, yet there are few studies on the specific cellular and molecular effects of microorganisms on the liver. Towards this aim, we constructed single-cell and spatial transcriptomic (ST) profiles of germ-free (GF) and specific pathogen-free (SPF) mice livers. The single cell RNA sequencing (scRNA-seq) found that the proportion of the vast majority of immune cells in GF mice was significantly reduced, especially natural killer T (NKT) cells, IgA plasma cells (IgAs), and Kupffer cells (KCs). The spatial enhanced resolution omics-sequencing (Stereo-seq) confirmed that microorganisms mediated the accumulation of Kupffer cells in the periportal zone. We also unexpectedly found that IgA plasma cells were more numerous and concentrated in the periportal vein in sections from SPF mice, while they were fewer and scattered in GF mice. ST technology also enables precise zonation of liver lobules into eight layers and three patterns based on gene expression level in each layer, allowing us to further investigate the effects of microbes on gene zonation patterns and functions. Furthermore, the untargeted metabolism experiments in the liver discovered that propionic acid levels were significantly lower in GF mice and may be related to the control of genes involved in bile acid and fatty acid metabolism. In conclusion, the combined study of scRNA-seq, Stereo-seq, and untargeted metabolomics revealed immune system defects as well as altered bile acid and lipid metabolic processes at the single-cell and spatial levels in the livers of GF mice. This study has great value for understanding host-microbiota interactions.

Contributor(s):Ruizhen Zhao.

Submitter:赵瑞珍(Ruizhen Zhao),technical support

Release date:2023-06-28

Updated:2024-10-16