Single-cell transcriptomic analysis reveals a novel cell state and switching genes during hepatic stellate cell activation in vitro

• Published in: Journal of translational medicine Vol. 20; no. 1; p. 53
• Main Authors: Wang, Hua, Zheng, Shaoping, Jiang, Hongbo, Wang, Xuejia, Zhou, Fengqin, Weng, Zhihong
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 29.01.2022; BioMed Central; BMC
• Subjects: Cell activation; Cell culture; Cluster analysis; Complications and side effects; Datasets; Development and progression; Extracellular matrix; Fatty liver; Fibroblasts; Fibrosis; Gene expression; Health aspects; Hepatic stellate cell; Hepatitis B; Liver; Liver diseases; Liver fibrosis; Ontology; Risk factors; RNA sequencing; Single-cell RNA sequencing; Transcriptomics; China; United States > US; Single-cell RNA sequencing; Hepatic stellate cell; Liver fibrosis
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/s12967-022-03263-4

The transformation of hepatic stellate cell (HSC) to myofibroblast is a key event during liver fibrogenesis. However, the differentiation trajectory of HSC-to-myofibroblast transition and the switching genes during this process remains not well understood. We applied single-cell sequencing data to reconstruct a single-lineage pseudotime trajectory of HSC transdifferentiation in vitro and analyzed the gene expression patterns along the trajectory. GeneSwitches was used to identify the order of critical gene expression and functional events during HSC activation. A novel cell state during HSC activation was revealed and the HSCs belonging to this state may be an important origin of cancer-associated fibroblasts (CAFs). Combining single-cell transcriptomics with GeneSwitches analyses, we identified some distinct switching genes and the order at which these switches take place for the new state of HSC and the classic culture-activated HSC, respectively. Based on the top switching genes, we established a four-gene combination which exhibited highly diagnostic accuracy in predicting advanced liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) or hepatitis B (HBV). Our study revealed a novel cell state during HSC activation which may be relevant to CAFs, and identified switching genes that may play key roles in HSC transdifferentiation and serve as predictive markers of advanced fibrosis in patients with chronic liver diseases.