ArticleCellular and molecular gastroenterology and hepatology2021
Single-Cell Transcriptomics Reveals Zone-Specific Alterations of Liver Sinusoidal Endothelial Cells in Cirrhosis.
Article in Cellular and molecular gastroenterology and hepatology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 143 papers.
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Who cites it
143 citing papers in PubMed, 203 citations in OpenAlex.
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- Regulatory roles and translational potential of the Kruppel-like factor family in liver disease.iLIVER · 2026Review
- Liver sinusoidal endothelial cells in liver diseases and hepatocellular carcinoma: molecular mechanisms, physiology, and therapies.Molecular biomedicine · 2026Review
- The Scavenger Function of LSECs, a Regulator of Liver Diseases.Current issues in molecular biology · 2026Review
- Hypoxia in MASLD: a spatial determinant of the pathogenesis.Trends in molecular medicine · 2026Review
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- Spatial hepatology: Decoding liver zonation for metabolic and regenerative therapeutics (Review).International journal of molecular medicine · 2026Review
- Liver sinusoidal endothelial cell fenestrations in metabolic liver disease: from molecular mechanisms to therapeutic perspectives.Cell communication and signaling : CCS · 2026Review
- Epigenetically controlled endothelial promyelocytic leukemia drives liver inflammation and fibrosis.The Journal of clinical investigation · 2026Article
- An LSEC-focused computational drug repurposing platform for liver fibrosis: Identification of vorinostat and other LSEC-protective candidates.bioRxiv : the preprint server for biology · 2026Article
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- Aging disrupts hepatocyte zonation homeostasis in mice and humans.Hepatology (Baltimore, Md.) · 2026Article
- Single-cell fixed RNA profiling uncovers SEMA4D and LMCD1 as therapeutic targets in a liver fibrosis model.JHEP reports : innovation in hepatology · 2026Article
- Spatiotemporal Transcriptomics Characterizes Immune Microenvironment During Mouse Liver Aging.Aging cell · 2026Article
- CXCL-CXCR2 signaling drives cancer-endothelium interactions in SCLC metastatic seeding.bioRxiv : the preprint server for biology · 2026Article
- A Novel 3D Visualization Method in Mice Identifies the Periportal Lamellar Complex (PLC) as a Key Regulator of Hepatic Ductal and Neuronal Branching Morphogenesis.bioRxiv : the preprint server for biology · 2026Article
83 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 1 institution in 2 countries.
Funding
Abstract
backgroundDysfunction of liver sinusoidal endothelial cells (LSECs) is permissive for the progression of liver fibrosis and cirrhosis and responsible for its clinical complications. Here, we have mapped the spatial distribution of heterogeneous liver ECs in normal vs cirrhotic mouse livers and identified zone-specific transcriptomic changes of LSECs associated with liver cirrhosis using scRNA-seq technology. APPROACH &
resultsCirrhosis was generated in endothelial specific green fluorescent protein (GFP) reporter mice through carbon tetrachloride inhalation for 12 weeks. GFP-positive liver EC populations were isolated from control and cirrhotic mice by FACS. We identified 6 clusters of liver EC populations including 3 clusters of LSECs, 2 clusters of vascular ECs and 1 cluster of lymphatic ECs. Based on previously reported LSEC-landmarks, we mapped the 3 clusters of LSECs in zones 1, 2, and 3, and determined phenotypic changes in each zone between control and cirrhotic mice. We found genes representing capillarization of LSECs (eg, CD34) as well as extracellular matrix genes were most upregulated in LSECs of zone 3 in cirrhotic mice, which may contribute to the development of basement membranes. LSECs in cirrhotic mice also demonstrated decreased expression of endocytic receptors, most remarkably in zone 3. Transcription factors (Klf2 [Kruppel-like factor-2], Klf4 [Kruppel-like factor-4], and AP-1) that induce nitric oxide production in response to shear stress were downregulated in LSECs of all zones in cirrhotic mice, implying increased intrahepatic vascular resistance.
conclusionThis study deepens our knowledge of the pathogenesis of liver cirrhosis at a spatial, cell-specific level, which is indispensable for the development of novel therapeutic strategies to target the most dysfunctional liver ECs.
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