{"title":"Single-cell and spatiotemporal transcriptomic analyses reveal the effects of microorganisms on immunity and metabolism in the mouse liver.","authors":"Ruizhen Zhao, Wei Cheng, Juan Shen, Weiming Liang, Zhao Zhang, Yifei Sheng, Tailiang Chai, Xueting Chen, Yin Zhang, Xiang Huang, Huanjie Yang, Chunqing Song, Li Pang, Cuoji Nan, Yangrui Zhang, Rouxi Chen, Junpu Mei, Hong Wei, Xiaodong Fang","doi":"10.1016/j.csbj.2023.06.020","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":46458,"journal":{"name":"Psychoanalytic Inquiry","volume":"39 1","pages":"3466-3477"},"PeriodicalIF":0.4000,"publicationDate":"2023-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10751235/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Psychoanalytic Inquiry","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.csbj.2023.06.020","RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/1/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"PSYCHOLOGY, PSYCHOANALYSIS","Score":null,"Total":0}
引用次数: 0
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.
期刊介绍：
Now published five times a year, Psychoanalytic Inquiry (PI) retains distinction in the world of clinical publishing as a genuinely monographic journal. By dedicating each issue to a single topic, PI achieves a depth of coverage unique to the journal format; by virtue of the topical focus of each issue, it functions as a monograph series covering the most timely issues - theoretical, clinical, developmental , and institutional - before the field. Recent issues, focusing on Unconscious Communication, OCD, Movement and and Body Experience in Exploratory Therapy, Objct Relations, and Motivation, have found an appreciative readership among analysts, psychiatrists, clinical psychologists and a broad range of scholars in the humanities.
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