Expression data comparing TMNK-1 to HMEC
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE60776 | GEO | 2014/12/01
SECONDARY ACCESSION(S): PRJNA259528
REPOSITORIES: GEO
Similar Datasets
Project description:Liver sinusoidal endothelial cells (LSECs) are specialized fenestrated scavenger endothelial cells involved in the elimination of modified plasma proteins and tissue turnover waste macromolecules from blood. LSECs also participate in liver immune responses. A challenge when studying LSEC biology is the rapid loss of the in vivo cell phenotype in culture. In this study, we have examined biological processes and pathways affected during early-stage primary culture of rat LSECs and checked for cell responses to the pro-inflammatory cytokine interleukin (IL)-1 and the anti-inflammatory drug dexamethasone. Methods: LSECs from male Sprague Dawley rats were cultured on type I collagen in a 5% oxygen atmosphere in DMEM with serum-free supplements for 2 and 24 h. Quantitative proteomics using tandem mass tag technology were used to examine proteins in cells and supernatants. Validation was done with ELISA and multiplex immunobead assays, cell ultrastructure was examined by scanning electron microscopy, and scavenger function by quantitative endocytosis assays. Results: LSECs cultured for 24 h showed a characteristic pro-inflammatory phenotype both in the presence and absence of IL-1, displaying upregulation of cellular responses to cytokines and interferon-, cell-cell adhesion, and glycolysis, and downregulation of membrane/endocytosis receptors (MCAM, STAB1, STAB2, LYVE1, CLEC4G) and proteins involved in pyruvate metabolism, citric acid cycle, fatty acid elongation, amino acid metabolism, and oxidation-reduction processes. Dexamethasone improved LSEC viability in culture and repressed the culture-induced stimulation of glycolysis, inflammatory and immune regulatory pathways, and secretion of pro-inflammatory cytokines while increasing IL-10 secretion compared to time-matched control. The number of sieve plates in LSECs was reduced at 24 h both in the presence and absence of dexamethasone but the dexamethasone-treated cells showed a more quiescent phenotype. Conclusion: Rat LSECs become activated towards a pro-inflammatory phenotype during early culture. Dexamethasone represses LSEC activation and improves cell viability.
2022-09-06 | PXD029241 | Pride
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.
2021-03-01 | GSE158988 | GEO
Project description:Liver sinusoidal endothelial cells (LSECs) and Kupffer cells (KCs) have important roles in liver homeostasis and host defense. Sharing the same microenvironment in the liver sinusoid, they form an effective scavenger cell system for removal of potentially harmful blood-borne substances. Unlike most other endothelia, LSECs are highly efficient in endocytosis of nanoparticles, including virus. Though controversial, LSECs have been reported to act as antigen presenting cells, thus contributing importantly to induction of immune tolerance in liver. There are also controversies about LSEC and KC specific markers, which may be due to overlapping cell functions, species differences, and/or problems with cell purification. We therefore used label-free proteomics to characterize and quantitatively compare proteome of freshly isolated, highly pure rat LSECs (SE-1/CD32b positive) and KCs (CD11b/c positive.We found that most immune genes expressed in KCs were also expressed in LSECs, albeit at a lower density, and they also have overlap in cell surface marker expression. Both cell types express high levels of scavenger receptors and immune lectins.
2020-11-11 | PXD012080 | Pride
Project description:The distinction between lymphatic and blood vessels is biologically fundamental. Two immortalized cell lines, which have been widely used as models for endothelial cells of blood vascular origin, are the human microvascular endothelial cell line-1 (HMEC-1) and the telomerase-immortalized microvascular endothelial cell line (TIME). However, analysis of protein expression by flow cytometry revealed expression of lymphatic markers on these cell lines. Furthermore, functional in vitro leukocyte transmigration assays demonstrated deficiencies in several steps of the leukocyte extravasation cascade. Hence we performed this microarray analysis of the gene expression in HMEC-1 and TIME. We then compare the expression profiles to those of published blood- and lymphatic endothelial cells.
2013-09-11 | GSE42216 | GEO
Project description:The distinction between lymphatic and blood vessels is biologically fundamental. Two immortalized cell lines, which have been widely used as models for endothelial cells of blood vascular origin, are the human microvascular endothelial cell line-1 (HMEC-1) and the telomerase-immortalized microvascular endothelial cell line (TIME). However, analysis of protein expression by flow cytometry revealed expression of lymphatic markers on these cell lines. Furthermore, functional in vitro leukocyte transmigration assays demonstrated deficiencies in several steps of the leukocyte extravasation cascade. Hence we performed this microarray analysis of the gene expression in HMEC-1 and TIME. We then compare the expression profiles to those of published blood- and lymphatic endothelial cells. Analysis of the gene expression profile of the immortalized human endothelial cell lines HMEC-1 and TIME to be compared to published primary blood- and lymphatic endothelial cells (see supplementary file linked below).
2013-09-11 | E-GEOD-42216 | biostudies-arrayexpress
Project description:Coagulation Factor VIII (FVIII) plays a pivotal role within the coagulation cascade, and deficiencies in its levels, as seen in Hemophilia A, can lead to significant health implications. Liver sinusoidal endothelial cells (LSECs) are the main producers and contributors of FVIII in blood, a fact we have previously elucidated through mRNA expression profiling when comparing these cells to other endothelial cell types. Our current investigation delves into small microRNAs, analyzing their distinct expression patterns across various endothelial cells and hepatocytes. The outcome of this exploration underscores the discernible microRNA expression differences that set LSECs apart from both hepatocytes (193 microRNAs at p < 0.05) and other endothelial cells (72 microRNAs at p < 0.05). Notably, the 134 and 35 overexpressed microRNAs in LSECs compared to hepatocytes and other endothelial cells, respectively, shed light on the unique functions of LSECs in the liver. Our investigation identified a panel of 10 microRNAs (miR-429, miR-200b-3p, miR-200a-3p, miR-216b-5p, miR-1185-5p, miR-19b-3p, miR-192-5p, miR-122-5p, miR-30c-2-3p, and miR-30a-5p) that distinctly define LSEC identity. Furthermore, our scrutiny extended to microRNAs implicated in F8 regulation, revealing a subset - miR-122-5p, miR-214-3p, miR-204-3p, and miR-2682-5p - whose expression intricately correlates with F8 expression within LSECs. This microRNA cohort emerges as a crucial modulator of F8, both directly through suppression and indirect effects on established F8-related transcription factors. The above miRNA emerged as potential targets for innovative therapies in Hemophilia A patients.
2024-02-19 | GSE242926 | GEO
Project description:Purpose: Endothelial cells respond to changes in subendothelial stiffness altering their proliferation, migration and barrier integrity but whether that is due to transcriptional reprogramming was largely unknown. Using RNA-Sequencing, we performed gene expression profiling for two endothelial cell types grown on soft or stiff matrices: primary human umbilical vein endothelial cells (HUVEC) and immortalized human microvascular endothelial cells (HMEC-1), to understand whether subendothelial stiffness-dependent changes in endothelial cell mechanics are due to transcriptional regulation. Methods and Results: By analyzing the differentially expressed genes between all samples we found that endothelial cell type rather that subendothelial stiffness is the primary determinant of the endothelial cell transcriptome. Both cell types respond to changes in their subendothelial stiffness by increasing the traction stresses they exert on stiffer as opposed to softer matrices, however it is apparently not the endothelial cell transcriptome that regulates this universal biomechanical response to subendothelial stiffness. Only a handful of genes were differentially expressed in each cell type in a stiffness-dependent manner, and none were shared between the two cell types examined. In contrast, thousands of genes were differentially regulated in HUVEC as compared to HMEC-1. HUVEC (but not HMEC-1) upregulate expression of TGF-2 on stiffer matrices, and also enhance their endogenous TGF-2 expression and their cell-matrix traction stresses in response to application of exogenous TGF-2. Conclusions: Altogether, these findings provide insights into the relationship between subendothelial stiffness, endothelial mechanics and variation of the transcriptome between distinct endothelial cell types, and reveal that subendothelial stiffness while critically impacting endothelial cell mechanics is minimally altering their transcriptome.
2019-07-31 | GSE135123 | GEO
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.
2015-05-07 | E-GEOD-67651 | biostudies-arrayexpress
Project description:Viruses lack the basic machinery needed to replicate and therefore must hijack host metabolism to propagate. Virus-induced metabolic alterations have yet to be systematically studied in the context of the host transcriptional regulation, offering insight into host-pathogen metabolic interplay. In this work we identified Hepatitis C Virus (HCV)-responsive regulators by coupling system-wide metabolic flux analysis with targeted perturbation of nuclear receptors in primary human hepatocytes. We find HCV-induced up-regulation of glycolysis, ketogenesis and drug metabolism, controlled by activation of HNF4α, PPARα, FXR and PXR, respectively. Pharmaceutical inhibition of HNF4α reversed HCV-induced glycolysis, blocking viral replication while increasing apoptosis in infected cells showing a viral-induced dependence on glycolysis. In contrast, pharmaceutical inhibition of PPARα or FXR reversed HCV-induced ketogenesis, but increased viral replication demonstrating a unique host anti-viral response. Our results show that viral-induced changes to host metabolism can be detrimental to its lifecycle demonstrating a distinct biological complexity. In this dataset, we include the expression data obtained from primary human hepatocyte oxygenated co-cultures infected or not infected by HCV and human sanp frozen liver biopsys from HCV patients at earley stages.
2016-10-07 | GSE84587 | GEO
Project description:BMP6 is an iron-sensing cytokine produced by liver sinusoidal endothelial cells (LSECs). The transcription factor NRF2 was proposed to induce Bmp6 expression in response to iron-triggered oxidative stress, and NRF2 knock-out mice were shown not capable of regulating Bmp6 in response to massive diet-imposed iron overload. However, LSEC Bmp6 expression levels in the hemochromatosis mouse model reflect hepatocytic, not endothelial iron content. Hence, it is not fully resolved how iron signals translate into alterations of Bmp6 mRNA levels. To further explore the mechanisms of Bmp6 regulation, we employed female mice aged 10-11 months that are hallmarked by hepatocytic, but not LSEC iron accumulation and decreased transferrin saturation, hinting at the absence of systemic iron overload. We found that LSECs of aged mice exhibit increased Bmp6 levels as compared to young controls, but do not show oxidative stress or a transcriptional signature characteristic of activated NFR2-mediated signaling in FACS-sorted LSECs. We further observed that primary murine LSECs derived from both wild-type and NRF2 knock-out mice induce Bmp6 in response to acute iron exposure. By analyzing RNA sequencing data of FACS-sorted LSECs from aged versus young mice, as well as upon acute injections of iron citrate in young mice, we identified ETS1 as a candidate transcription factor involved in Bmp6 regulation. By conducting siRNA-mediated knock-down and small-molecule treatments in primary LSECs, we show that Bmp6 transcription is regulated in an NRF2-independent manner via ETS1, which is activated downstream of p38 MAP kinase-mediated signaling. This knowledge expands the understanding of Bmp6 transcriptional control in both iron-triggered oxidative stress and under the conditions uncoupled to LSECs reactive oxygen species levels.
2024-01-25 | GSE235975 | GEO