Bulk RNA-seq analysis of control and siMPI TWNT-4 cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE193844 | GEO | 2022/03/23
REPOSITORIES: GEO
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Project description:Bacillus subtilis has different response systems to cope with external and internal stressors. In this study, we investigated the effect of phosphosugar stress caused by accumulation of phosphosugars in B. subtilis. To do so, manA, the encoding gene of mannose-6-phosphate isomerase, was deleted in B. subtilis KM0 to construct strain KM642. Next, strains KM0 and KM642 were cultured in LB with 1% mannose and the cell pellets were isolated after 3.5 h of incubation at 37 °C for transcriptome analysis by RNA-Seq. Differential gene expression analysis was performed based on the RNA-Seq data generated by paired end sequencing (2 x 75nt read length) of Illumina TruSeq stranded mRNA-cDNA libraries on Illumina MiSeq system from control strain and manA deletion mutant.
2019-06-06 | E-MTAB-7262 | biostudies-arrayexpress
Project description:This study explored the regulatory effect of D-mannose on host immunometabolic responses after viral infection. The results showed that D-mannose can compete with glucose for transporters and hexokinase, inhibiting glycolysis, reducing mitochondrial reactive oxygen species and succinate-induced HIF-1α, thereby reducing virus-induced inflammatory cytokine production. Even with delayed combinatorial treatment of D-mannose and antiviral monotherapy after viral infection, a synergistic effect was still observed in mouse models. Phosphomannose isomerase (PMI) activity determines the benefits of D-mannose, as simultaneous PMI depletion and mannose supplementation impaired cell viability. PMI inhibition can suppress replication of various viruses by affecting host and viral surface protein glycosylation. However, D-mannose does not inhibit PMI activity or viral fitness. In summary, PMI-centered therapeutic strategies can eliminate viral infections, while D-mannose treatment reprograms glycolysis to control collateral damage.
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Project description:Background & Aims: Rapid induction of beta-PDGF receptor (beta-PDGFR) is a core feature of hepatic stellate cell activation, the hallmark of liver fibrogenesis. However, biological consequences of the induction are not well characterized. We aimed to determine the involvement of beta-PDGFR-mediated molecular pathway activation on hepatic stellate cells in liver injury, fibrogenesis, and carcinogenesis in vivo. Methods: Loss and constitutive activation of beta-PDGFR were assessed in mouse models with either a stellate cell-specific beta-PDGFR knockout or the expression of an autoactivating mutation respectively. Liver injury and fibrosis were induced in two mechanistically distinct models: carbontetrachloride (CCl4) treatment and ligation of the common bile duct. Hepatocarcinogenesis with underlying liver injury/fibrosis was assessed by a single dose of diethylnitrosamine (DEN) followed by repeated injections of CCl4. Genome-wide expression profiling was performed isolated stellate cells from these models to determine deregulated pathways. Results: Depletion of beta-PDGFR in hepatic stellate cells led to decreased histological liver injury, serum transaminases, collagen alpha 1(I) and alpha smooth muscle actin expression, and collagen deposition. Stellate cell proliferation was significantly reduced after acute hepatic injury in vivo. In contrast, autoactivation of beta-PDGFR in stellate cells accelerated liver fibrosis, most prominently after 6 weeks of CCl4 induced injury. There was no difference in development of DEN-induced pre-neoplastic loci according to the status of beta-PDGFR. Conclusions: Depletion of beta-PDGFR in hepatic stellate cells attenuated the development of liver injury, fibrosis, and stellate cell proliferation in multiple animal models, whereas the constitutive activation of beta-PDGFR enhanced fibrosis. However, manipulation of beta-PDGFR alone did not reduce development of dysplastic nodules. These findings indicate that titration of receptor beta-PDGFR expression on stellate cells parallels fibrosis and injury, but may not impact the development of hepatic neoplasia alone. Hepatic stellate cells were isolated from liver of beta-PDGFR-wild-type or knockout mice, and treated with beta-PDGF ligand or vehicle control.
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Project description:Liver fibrosis is the excessive accumulation of extracellular matrix that can progress to cirrhosis and failure if untreated. The mechanisms of fibrogenesis are multi-faceted and remain elusive with no approved antifibrotic treatments available. Here we use single-cell RNA sequencing (scRNA-seq) of the adult zebrafish liver to study the molecular and cellular dynamics of the liver at a single-cell level and demonstrate the value of the adult zebrafish as a model for studying liver fibrosis. scRNA-seq reveals transcriptionally unique populations of hepatic cell types that comprise the zebrafish liver. Joint clustering with human liver scRNA-seq data demonstrates high conservation of transcriptional profiles and human marker genes in zebrafish cell types. Human and zebrafish hepatic stellate cells (HSCs), the driver cell in liver fibrosis, specifically show conservation of transcriptional profiles and we uncover Colec11 as a novel, conserved marker for zebrafish HSCs. To demonstrate the power of scRNA-seq to study liver fibrosis, we performed scRNA-seq on our zebrafish model of a pediatric liver disease with characteristic early, progressive liver fibrosis caused by mutation in mannose phosphate isomerase (MPI). Comparison of differentially expressed genes from human and zebrafish MPI mutant HSC datasets demonstrated similar activation of fibrosis signaling pathways and upstream regulators. CellPhoneDB analysis revealed important receptor-ligand interactions within normal and fibrotic states. This study establishes the first scRNA-seq atlas of the adult zebrafish liver, highlights the high degree of similarity to the human liver, and strengthens its value as a model to study liver fibrosis.
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Project description:Background & Aims: Rapid induction of beta-PDGF receptor (beta-PDGFR) is a core feature of hepatic stellate cell activation, the hallmark of liver fibrogenesis. However, biological consequences of the induction are not well characterized. We aimed to determine the involvement of beta-PDGFR-mediated molecular pathway activation on hepatic stellate cells in liver injury, fibrogenesis, and carcinogenesis in vivo. Methods: Loss and constitutive activation of beta-PDGFR were assessed in mouse models with either a stellate cell-specific beta-PDGFR knockout or the expression of an autoactivating mutation respectively. Liver injury and fibrosis were induced in two mechanistically distinct models: carbontetrachloride (CCl4) treatment and ligation of the common bile duct. Hepatocarcinogenesis with underlying liver injury/fibrosis was assessed by a single dose of diethylnitrosamine (DEN) followed by repeated injections of CCl4. Genome-wide expression profiling was performed isolated stellate cells from these models to determine deregulated pathways. Results: Depletion of beta-PDGFR in hepatic stellate cells led to decreased histological liver injury, serum transaminases, collagen alpha 1(I) and alpha smooth muscle actin expression, and collagen deposition. Stellate cell proliferation was significantly reduced after acute hepatic injury in vivo. In contrast, autoactivation of beta-PDGFR in stellate cells accelerated liver fibrosis, most prominently after 6 weeks of CCl4 induced injury. There was no difference in development of DEN-induced pre-neoplastic loci according to the status of beta-PDGFR. Conclusions: Depletion of beta-PDGFR in hepatic stellate cells attenuated the development of liver injury, fibrosis, and stellate cell proliferation in multiple animal models, whereas the constitutive activation of beta-PDGFR enhanced fibrosis. However, manipulation of beta-PDGFR alone did not reduce development of dysplastic nodules. These findings indicate that titration of receptor beta-PDGFR expression on stellate cells parallels fibrosis and injury, but may not impact the development of hepatic neoplasia alone.
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Project description:Gene expression of mouse hepatic stellate cells was characterized under the following conditions: Quiescent (isolated from normal mouse liver) and reverted (isolated from mouse liver treated with 4 injections of carbontetrachloride followed by 45 day rest period) Affymetrix Mouse 1.0ST gene expression measurements were used to characterize the transcriptomic basis in quiescent hepatic stellate cells, isolated from normal liver, and reverted hepatic stellate cells, isolated from liver treated with 4 injections of CCl4 followed by a 45 day rest period. Gene expression of mouse hepatic stellate cells was characterized under the following conditions: A. Quiescent control hepatic stellate cells (n=4). B. Reverted hepatic stellate cells (n=4).
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