Liver zonation is fundamental to normal liver function, and numerous studies have investigated the microstructure of normal liver lobules. However, only a few studies have explored the zonation signature in hepatocellular carcinoma (HCC). In this study, we investigated the significance of liver zonation in HCC with the help of single-cell RNA sequencing (scRNA-seq) and multicolor immunofluorescence staining. Liver zonation-related genes were extracted from the literature, and a three-gene model was established for HCC prognosis. The model reliability was validated using bulk RNA and single-cell RNA-level data, and the underlying biological mechanism was revealed by a functional enrichment analysis. The results showed that the signaling pathways of high-risk groups were similar to those of perivenous zones in the normal liver, indicating the possible regulating role of hypoxia in HCC zonation. Furthermore, the co-staining results showed that the low-grade tumors lost their zonation features whereas the high-grade tumors lost the expression of zonation-related genes, which supported the results obtained from the sequencing data.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9260020 | PMC |
| http://dx.doi.org/10.3389/fcell.2022.806408 | DOI Listing |
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- The liver comprises several key cell types, including hepatocytes, endothelial cells, Kupffer cells, and hepatic stellate cells, which work together to maintain liver health and function.
- Research using genetically modified mice showed that hepatic stellate cells are the primary producers of the signaling molecules GDF2 and BMP10 in the liver.
- The study revealed that these molecules support the differentiation of Kupffer and endothelial cells, while disruptions in their signaling can lead to activation of hepatic stellate cells and conditions like liver fibrosis and iron overload.
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