Project description:Hepatocellular carcinoma (HCC), the fourth leading cause of cancer mortality, develops almost exclusively in patients with chronic liver disease (CLD) and advanced fibrosis. Here we interrogated functions of hepatic stellate cells (HSC), the main source of liver fibroblasts, during hepatocarcinogenPesis. Genetic depletion, activation or inhibition established HSC as tumour-promoting in mouse models of HCC. HSC were enriched in the preneoplastic environment, where they closely interacted with hepatocytes and modulated hepatocarcinogenesis by regulating hepatocyte proliferation and death. Analysis of mouse and human HSC subpopulations and their associated mediators by single cell RNA-sequencing in conjunction with genetic ablation revealed dual functions of HSC in hepatocarcinogenesis. Hepatocyte growth factor, enriched in quiescent and cytokine-producing HSC (cyHSC), protected from hepatocyte death and HCC development. In contrast, type I collagen, enriched in activated myofibroblastic HSC (myHSC), promoted proliferation and tumour development via increased stiffness and TAZ activation in pretumoural hepatocytes and via activation of discoidin domain receptor 1 in established tumours. An increasing HSC dysbalance between cyHSC and myHSC during liver disease progression was associated with elevated HCC risk in patients. In summary, the dynamic shift of HSC subpopulations and their mediators during CLD is associated with a switch from HCC protection to HCC promotion.
Project description:We report the application of RNA sequencing technology for high-throughput profiling in HCC tissues. In the present study, to explore novel biomarkers of HCC, we firstly explored the expression profiles of mRNAs and miRNAs in three pairs of HCC patients (tumor tissues and non-tumorous tissues) by high-throughput RNA sequencing. A total of 1024 mRNAs were found to be significantly dysregulated (636 up-regulated and 388 down-regulated), 50 miRNAs were found to be significantly dysregulated (27 up-regulated and 23 down-regulated) in the HCC tissues compared with the non-tumorous tissues.Then validae the differentially expressed miRNAs by qRT-PCR in HCC tissues and serum. This study provides a framework for the application of miRNAs to be ideal biomarkers for HCC.
Project description:To determine the circRNA expression profile in HCC and matched non-tumor tissues, we used circRNA microArray analysis form Arraystar to examine the expression of circRNAs in HCC and matched non-tumor tissues.
Project description:circRNA microArray analysis from Arraystar were used to examine the expression profile in HCC with metastasis, HCC without metastasis, and non-tumor tissues
Project description:We performed single-nuclei RNAseq of Sprague Dawley rat area postrema and nucleus tractus solitarius brain samples to identify cellular subtypes.
Project description:We performed single-nuclei RNAseq of Brown Norway rat nucleus accumbens after a single injection of morphine or after morhpine self-administration