Key genes in the liver fibrosis process are mined based on single-cell transcriptomics

Abstract

At present, there is no effective treatment for liver fibrosis, and treatment options are limited. Liver fibrosis remains a cancer with a high mortality rate. During liver injury, hepatic stellate cells transdifferentiate into myofibroblasts capable of proliferation, migration, and invasion. The transcriptomes of more than 60,000 human single cells were analyzed in 9 cirrhotic tissue samples and 11 normal liver tissue samples in order to identify key regulatory factors and core driver genes for myofibroblast transformation. Through cell communication analysis, we obtained the key cytokines of hepatic stellate cells regulating myofibroblasts, such as PDGFA, PDGFAR, PGF, NTF3, etc. At the same time, we also obtained key driver genes related to myofibroblast characteristics, such as LUM,GGT5, RBP1, ASPN,DCN, etc., through single-nucleus consensus weighted gene co-expression network analysis (scWGCNA). In addition, since APOE also plays a very important role in myofibroblasts, we also explored the driver genes associated with APOE, such as THY1,MMP2,COL3A1, etc. We analyzed the core driver gene of hepatic stellate cell transformation into myofibroblasts at the single-cell level in the process of liver fibrosis, providing valuable information for the future targeted gene diagnosis and treatment of liver fibrosis.