Project description:Primary human liver sinusoidal endothelial cells from 7 explanted livers were incubated in conditioned media from IMR90 cells undergoing several forms of senescence
Project description:Comparison of C57BL/6J 8-10 weeks male mouse liver sinusoidal endothelial cells (LSEC) from normal liver and from liver injured by carbon tetrachloride administration. Keywords: other
Project description:Aging-associated transcriptome changes in liver sinusoidal endothelial cells. RNA was prepared from liver sinusoidal endothelial cells of the male 8 weeks and 24 months old C57BL/6J mice.RNA samples were then subjected to RNA-sequencing and gene expression profiling analysis.
Project description:To identify leukocyte adhesion receptors which differentially regulate recruitment in human liver sinusoidal endothelial cells compared to a protoptypic venular endothelium Gene expression was measured in four groups Group 1: cultured human liver sinusoidal endothelial cells (HSEC) Group 2: cultured human umbilical vein endothelial cells (HUVEC) Group3: Interferon gamma and tumour necrosisfactor alpha treated HSEC and Group 4: Interferon gamma and tumour necrosisfactor alpha treated HUVEC. Two replicates were used for each group.
Project description:Two of the most highly abundant transcripts in liver sinusoidal endothelial cells are Stab1 and Stab2, we investigated downstream effects on liver sinusoidal endothelial cells by disrupting their expression. We used microarrays to detail the global programme of gene expression in liver sinusoidal endothelial cells deficient for Scavenger-Receptor type H compared to Wildtype.
Project description:Comparison of C57BL/6J 8-10 weeks male mouse liver sinusoidal endothelial cells (LSEC) from normal liver and from liver injured by carbon tetrachloride administration. Keywords: other
Project description:Portal hypertension (PHTN) is a severe complication of liver cirrhosis. It is associated with intrahepatic sinusoidal remodeling induced by sinusoidal resistance and angiogenesis. Collagen type IV (COL4), a major component of basement membrane (BM), forms in liver sinusoids upon chronic liver injury. However, the cellular source and transcriptional regulation of COL4, as well as how it progresses in liver diseases is unknown. Here, we examined how COL4 is produced and how it regulates sinusoidal remodeling in PHTN. RNA-seq analysis on human cirrhotic livers revealed an increase in COL4 expression, which was further confirmed via immunofluorescence (IF) staining. scRNA-seq analysis identified Liver sinusoidal endothelial cells (LSECs) as the predominant source of COL4 expression in mouse liver, which was upregulated in a TNFα-NFκB dependent manner. Epigenetic repression of enhancer-promoter interaction silences COL4 gene expression via dCas9-KRAB-mediated epigenome editing approach. LSEC-specific COL4 mutation or repression abrogated sinusoidal resistance and angiogenesis, thereby alleviated sinusoidal remodeling and PHTN. Our findings reveal LSECs as a major source of COL4 in the liver which plays a prominent role in sinusoidal remodeling and PHTN.
Project description:Liver sinusoidal endothelial cells (LSEC) are unique endothelial cell typelining the sinusoids of the liver and we have shown that these cells respond in a unique matter when exposed to saturated and unsaturated free fatty acids (FFA) and bile acids. We used microarray to analyze the transcriptional differences between the LSEC exposed to free fatty acids and bile acid receptor agonists to further shed light on their role in non-alcoholic fatty liver disease. The Murine Liver Sinusoidal Endothelial Cell Line (TSEC) was treated with palmitic and oleic acid or the bile acid receptor agonist INT-767 for 8 hours. Total RNA was then harvested to determine transcriptional differences.
Project description:Chronic liver disease is a major leading cause of portal hypertension that affects approximately 1.5 billion people globally. We show that GIMAP5, a small organellar GTPase, is selectively expressed in liver endothelial cells and human GIMAP5 deficiency causes portal hypertension with capillarization of liver sinusoidal endothelial cells (LSECs). LSEC capillarization is recapitulated in GIMAP5 loss-of-function (LOF) mice, and upon conditional Gimap5 deletion in endothelial cells. Single cell RNA-sequencing analyses reveals replacement of LSECs with capillarized endothelial cells and expansion of liver lymphatic endothelial cells in GIMAP5 LOF mice, and places GIMAP5 upstream of GATA4, a transcription factor required for LSEC-specification. Our studies reveal that GIMAP5 prevents portal hypertension by maintaining LSEC identity and suggest that LSEC is an induced endothelial cell state.
Project description:Transcriptomic analysis of VEGF-A stimulated liver sinusoidal endothelial cell gene expression. Untreated cells were compared to those treated with VEGF-A. VEGF-A stimulation is critical for normal LSEC phenotype, and the response to liver injury Two conditions: untreated vs. VEGF-A treated. LSEC from 2 donors were pooled. 4 technical repeats.