Liver in infections: a single-cell and spatial transcriptomics perspective

Abstract

The liver is an immune organ that plays a vital role in the detection, capture, and clearance of pathogens and foreign antigens that invade the human body. During acute and chronic infections, the liver transforms from a tolerant to an active immune state. The defence mechanism of the liver mainly depends on a complicated network of intrahepatic and translocated immune cells and non-immune cells. Therefore, a comprehensive liver cell atlas in both healthy and diseased states is needed for new therapeutic target development and disease intervention improvement. With the development of high-throughput single-cell technology, we can now decipher heterogeneity, differentiation, and intercellular communication at the single-cell level in sophisticated organs and complicated diseases. In this concise review, we aimed to summarise the advancement of emerging high-throughput single-cell technologies and re-define our understanding of liver function towards infections, including hepatitis B virus, hepatitis C virus, Plasmodium, schistosomiasis, endotoxemia, and corona virus disease 2019 (COVID-19). We also unravel previously unknown pathogenic pathways and disease mechanisms for the development of new therapeutic targets. As high-throughput single-cell technologies mature, their integration into spatial transcriptomics, multiomics, and clinical data analysis will aid in patient stratification and in developing effective treatment plans for patients with or without liver injury due to infectious diseases.

Heat Inactivation of Nipah Virus for Downstream Single-Cell RNA Sequencing Does Not Interfere with Sample Quality

“…The development of high-throughput sequencing technologies has made it possible to determine the transcriptomic landscape at a single cell level. As for viral infection studies, single-cell RNA sequencing (scRNA-seq) does not only allow for discrimination between infected and non-infected bystander cells, but it also provides insight into cell typespecific responses in tissue culture as well as complex organs and immune systems [1][2][3]. However, the more stringent biosafety requirements using highly pathogenic viruses have hindered scRNA-seq analysis in studies involving viruses handled at the highest specific responses in tissue culture as well as complex organs and immune systems [1][2][3].…”

“…As for viral infection studies, single-cell RNA sequencing (scRNA-seq) does not only allow for discrimination between infected and non-infected bystander cells, but it also provides insight into cell typespecific responses in tissue culture as well as complex organs and immune systems [1][2][3]. However, the more stringent biosafety requirements using highly pathogenic viruses have hindered scRNA-seq analysis in studies involving viruses handled at the highest specific responses in tissue culture as well as complex organs and immune systems [1][2][3]. However, the more stringent biosafety requirements using highly pathogenic viruses have hindered scRNA-seq analysis in studies involving viruses handled at the highest biosafety level, BSL-4.…”

Single‐cell RNA sequencing reveals reduced intercellular adhesion molecule crosstalk between activated hepatic stellate cells and neutrophils alleviating liver fibrosis in hepatitis B virus transgenic mice post menstrual blood‐derived mesenchymal stem cell transplantation

“… 21 , 22 scRNA‐seq has enabled the study of various cell subpopulations, molecular processes, and interactions among different cell types in liver parenchymal cells, such as hepatocytes, cholangiocytes, and liver nonparenchymal cells (NPCs), including LSECs, HSCs, Kupffer cells, myofibroblasts/fibroblasts, and other immune cells. 23 , 24 , 25 , 26 Advances in single‐cell phenotyping have allowed the cellular classification of the origins of myofibroblasts during fibrosis under different disease conditions and the corresponding functional in‐depth dissections. 27 , 28 Activation from quiescent HSCs (qHSCs) to aHSCs has been extensively studied in liver fibrosis models using scRNA‐seq.…”