Similar Datasets
Project description:Myc and its target Odc1 were among the most 250 strongly upregulated genes in Dll4 mutant ECs, compared with Notch1 and Rbpj mutants. Myc is known to activate important ribosome biogenesis and protein translation pathways, favoring cell growth. Dll4iDEC livers showed upregulation of a large range of canonical E2F, Myc, and mTORC1 target genes and ribosomal genes, particularly in the activated, proliferating, and endothelial tip-cell clusters. This hypermetabolic transcriptional status was confirmed by in-depth proteomics analysis of protein lysates obtained from freshly isolated liver ECs, providing the first proteomics analysis of the endothelial tip-cell state induced by targeting Dll4.
2023-04-11 | PXD041349 | Pride
Project description:Dysfunction of liver endothelial cells (ECs), especially sinusoid endothelial cells (LSECs), play a key role in progression of liver fibrosis/cirrhosis. Here, we reported a map which reveals heterogeneity and spatial distribution of liver ECs in normal versus cirrhotic mouse liver and determined liver zonal specific transcriptomic changes of LSECs associated with liver cirrhosis using single-cell RNA sequencing technology. We identified 6 clusters of liver EC populations including 3 clusters of LSECs, 2 clusters of vascular ECs (arterial and central venous ECs) and 1 cluster of lymphatic ECs. Particularly, we mapped the 3 clusters of LSECs in Zone1-3. We found that liver EC identities are conserved even in liver cirrhosis and that Zone3 LSECs are most susceptible to damages associated with liver cirrhosis with increased capillarization and decreased abilities to regulate endocytosis and vascular tone. Altogether, this study deepens our knowledge for the pathophysiology of cirrhosis at a spatial and cell-specific level, which are indispensable for the development of novel therapeutic strategies to target liver ECs.
2021-02-05 | GSE147581 | GEO
Project description:Endothelial cells (ECs) can detect oxygen and nutrient shortages in tissues and are able to adapt by inducing proliferation and migration into ischemic areas. Here, we present results that elucidate the striking role of a novel, EC/mural cell-specific gene, Apold1, in regulating pathological angiogenesis in ischemia. Screening of the transcriptomic profile by bulk RNAseq of wild type (WT) and Apold1-/- isolated muscle endothelial cells (ECs) revealed minor transcriptional differences upon Apold1 knockout. In contrast RNA sequencing on primary ECs derived from Apold1-/- or WT ECs, which were briefly (16 hrs) cultured in angiogenic medium, showed striking differences.
2023-09-12 | GSE217694 | GEO
Project description:Analysis of brown adipose tissue (BAT) isolated from wildtype (WT) and liver kinase B1 (LKB1) deletion mice (Ad/LKB1). Results provide insight into molecular mechanisms underlying paralysis of Ad/LKB1 mice
2017-11-01 | GSE89348 | GEO
Project description:Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers with a high level of liver metastasis. Despite substantial advances, resistance to therapy, including gemcitabine, is still a major obstacle to improved progression free survival. Recent studies have indicated that endothelial cell (EC) focal adhesion kinase (FAK) regulates DNA-damaging therapy induced angiocrine factors and chemosensitivity in malignant cells. However, the effect of EC-FAK regulated angiocrine signalling in chemosensitivity of metastatic PDAC remains unexplored. Here, we show that inducible loss of EC-FAK in both orthotopic and spontaneous mouse models of PDAC reduces liver metastasis and improves survival rates in gemcitabine treated, but not untreated, mice, without affecting primary tumour growth, tumour vascularization, blood vessel leakage or early metastatic events. Phosphoproteomics analysis show a downregulation of the MAPK/ RAF/ PAK signalling pathways in gemcitabine treated FAK-depleted ECs compared to gemcitabine treated WT ECs. Moreover, low levels of EC-FAK correlate with increased survival and reduced relapse in gemcitabine treated human PDAC patients, supporting the clinical relevance of our findings. Altogether, we have identified a new role of EC-FAK regulating PDAC liver metastasis upon gemcitabine treatment that impacts on survival.
2023-03-10 | PXD021542 | Pride
Project description:The hematopoietic stem cell (HSC) niche has been extensively studied in bone marrow, yet a more systematic investigation into the microenvironment regulation of hematopoiesis in fetal liver is necessary. Here we investigate the spatial organization and transcriptional profile of individual cells in both wild type and Tet2-/- fetal livers, by multiplexed error robust fluorescence in situ hybridization (MERFISH). We find that specific pairs of fetal liver cell types are preferentially positioned next to each other. Ligand-receptor singling molecule pairs such as Kitl and Kit are enriched in neighboring cell types. The majority of HSCs are directly in contact with endothelial cells (ECs) in both wild type and Tet2-/- fetal livers. Loss of Tet2 increases the number of HSCs, and upregulates Wnt and Notch signaling genes in the HSC niche. Two subtypes of ECs – arterial ECs and sinusoidal ECs – and other cell types contribute distinct signaling molecules to the HSC niche. Collectively, this study provides a comprehensive picture and bioinformatic foundation for HSC spatial regulation in fetal liver.
2021-04-16 | GSE172127 | GEO
Project description:The hematopoietic stem cell (HSC) niche has been extensively studied in bone marrow, yet a more systematic investigation into the microenvironment regulation of hematopoiesis in fetal liver is necessary. Here we investigate the spatial organization and transcriptional profile of individual cells in both wild type and Tet2-/- fetal livers, by multiplexed error robust fluorescence in situ hybridization (MERFISH). We find that specific pairs of fetal liver cell types are preferentially positioned next to each other. Ligand-receptor singling molecule pairs such as Kitl and Kit are enriched in neighboring cell types. The majority of HSCs are directly in contact with endothelial cells (ECs) in both wild type and Tet2-/- fetal livers. Loss of Tet2 increases the number of HSCs, and upregulates Wnt and Notch signaling genes in the HSC niche. Two subtypes of ECs – arterial ECs and sinusoidal ECs – and other cell types contribute distinct signaling molecules to the HSC niche. Collectively, this study provides a comprehensive picture and bioinformatic foundation for HSC spatial regulation in fetal liver.
2021-04-16 | GSE172128 | GEO
Project description:A resident vascular endothelial stem cell (VESC) population expressing CD157 and CD200 has been identified recently in the adult mouse. However, the origin of this population and how it develops has not been characterized, nor has it been determined whether VESC-like cells are present during the perinatal period. Here, we investigated the presence of perinatal VESC-like cells and their relationship with the adult VESC-like cell population. We applied single-cell RNA sequencing of endothelial cells (ECs) from embryonic stage liver and investigated transcriptomic changes during liver EC development. We performed flow cytometry, immunofluorescence, colony formation assays and transplantation assays to validate the presence of and to assess the function of CD157+ and CD200+ endothelial cells (ECs) in the perinatal period. We identified CD200-expressing VESC-like cells in the perinatal period. These cells formed colonies in vitro and had high proliferative ability. The RNA Velocity tool and transplantation assay results indicated that the projected fate of this population was towards adult VESC-like cells expressing CD157 and CD200 one week after birth. Our study provides a comprehensive atlas of liver EC development and documents VESC-like cell lineage commitment at single-cell resolution.
2023-08-18 | GSE231545 | GEO
Project description:Expression of the Zinc-Finger E-Box-binding Homeobox (Zeb)2 is enriched in Liver Sinusoidal Endothelial cells (LSECs), but its role in liver ECs remains unknown. We performed RNA sequencing on the main liver cell types from wild-type mice and mice lacking Zeb2 specifically in endothelial cells to identify cell-autonomous and non-autonomous RNA expression changes and to find pathways and GO-terms affected by genetic Zeb2 inactivation.
2022-03-30 | GSE150699 | GEO
Project description:Endothelial cells from nine steady state tissues and two regenerating tissues (bone marrow and liver) were intravitally labeld, isolated via flow sorting, and immediately processed for RNA extraction. When of sufficient quality, the RNA was amplified and hybridized. For comparison, Human Emybryonic Stem Cell-derived Endothelial cells (hESC-ECs) were differentiated and isolated based on similarities to the adult mouse counterparts.
2013-07-15 | GSE47067 | GEO