[PDF] Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches | Semantic Scholar (2024)

The first comprehensive atlas of the PSC liver is presented and hyper-activation and exhaustion-like phenotypes of myeloid cells and markers of chronic cytokine expression in late-stage PSC lesions are demonstrated.

The article provides a comprehensive overview of the technical innovations and bioinformatics strategies that underpin spatial transcriptome analysis and points to the immense promise these technologies hold for identifying new therapeutic targets and advancing personalized medicine in hepatology, despite the hurdles in widespread adoption and standardization.

An advanced, age-dependent polarization state of SPP1+ macrophages in fibrotic tissues as a result of prolonged inflammatory cues within each tissue microenvironment is suggested.

It is indicated that chronic injury creates an environment that induces cellular plasticity in human organs, and understanding the underlying mechanisms of this process could open new therapeutic avenues in the management of chronic diseases.

This integrative study dissects in detail the molecular gradients controlling liver cell function, systematically defining how gene networks are dynamically modulated through intercellular communication to promote regeneration.

It is demonstrated that spatial transcriptomes of parenchymal and fibrotic liver regions express unique gene content within cirrhotic liver and demonstrate proof of concept that spatial transcriptsomes combined with additional RNA sequencing methodologies can refine the localization of gene content and cell lineages in the search for antifibrotic targets.

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A spatial proteogenomic atlas of the healthy human and murine liver combining single-cell CITE-seq, single-nuclei sequencing, spatial transcriptomics and spatial proteomics is presented, revealing the conserved program of bona fide Kupffer cells and bile-duct macrophages.

It is shown that the EPCAM+ population is heterogeneous, comprising hepatocyte-biased and cholangiocyte populations as well as a TROP2int progenitor population with strong potential to form bipotent liver organoids.

The transcriptomes of more than 100,000 single human cells are profile, yielding molecular definitions for non-parenchymal cell types that are found in healthy and cirrhotic human liver, and unanticipated aspects of the cellular and molecular basis of human organ fibrosis are dissected at a single-cell level.

This work measures the entire transcriptome of thousands of mouse liver cells and infer their lobule coordinates on the basis of a panel of zonated landmark genes, characterized with single-molecule fluorescence in situ hybridization and finds that around 50% of liver genes are significantly zonation and uncover abundant non-monotonic profiles that peak at the mid-lobule layers.

Data reveal that liver sinusoidal endothelial cells sense the microbiome, actively orchestrating the localization of immune cells, to optimize host defence, and provide evidence that immune zonation is required to protect the host from the dissemination of blood-borne pathogens.

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