ArticleComputational and structural biotechnology journal2023
Single-cell and spatiotemporal transcriptomic analyses reveal the effects of microorganisms on immunity and metabolism in the mouse liver.
Article in Computational and structural biotechnology journal, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 7 citations in OpenAlex.
- Sesamin Ameliorates High-Sugar, High-Fat Diet-Induced Hepatic Dysfunction via CYP1A2-Mediated Regulation of Lipid Metabolism and Oxidative Stress.Journal of cellular and molecular medicine · 2026Article
- Integrating microbial GWAS and single-cell transcriptomics reveals associations between host cell populations and the gut microbiome.Nature microbiology · 2025Article
- Article
- Single-cell transcriptomics unveiled that early life BDE-99 exposure reprogrammed the gut-liver axis to promote a proinflammatory metabolic signature in male mice at late adulthood.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
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Authors and funding
19 authors at 5 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
The gut-liver axis is a complex bidirectional communication pathway between the intestine and the liver in which microorganisms and their metabolites flow from the intestine through the portal vein to the liver and influence liver function. In a sterile environment, the phenotype or function of the liver is altered, but few studies have investigated the specific cellular and molecular effects of microorganisms on the liver. To this end, we constructed single-cell and spatial transcriptomic (ST) profiles of germ-free (GF) and specific-pathogen-free (SPF) mouse livers. Single-cell RNA sequencing (scRNA-seq) and single-nucleus RNA sequencing (snRNA-seq) revealed that the ratio of most immune cells was altered in the liver of GF mice; in particular, natural killer T (NKT) cells, IgA plasma cells (IgAs) and Kupffer cells (KCs) were significantly reduced in GF mice. Spatial enhanced resolution omics sequencing (Stereo-seq) confirmed that microorganisms mediated the accumulation of Kupffer cells in the periportal zone. Unexpectedly, IgA plasma cells were more numerous and concentrated in the periportal vein in liver sections from SPF mice but less numerous and scattered in GF mice. ST technology also enables the precise zonation of liver lobules into eight layers and three patterns based on the gene expression level in each layer, allowing us to further investigate the effects of microbes on gene zonation patterns and functions. Furthermore, untargeted metabolism experiments of the liver revealed that the propionic acid levels were significantly lower in GF mice, and this reduction may be related to the control of genes involved in bile acid and fatty acid metabolism. In conclusion, the combination of sc/snRNA-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 will be of great value for understanding host-microbiota interactions.
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