Transcriptomes of the metabolism inhibited mouse embryonic stem cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE140712 | GEO | 2022/11/20
REPOSITORIES: GEO
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Project description:Pulmonary macrophages have two distinct ontogenies: long-lived embryonically-seeded alveolar macrophages (AM) and bone marrow-derived macrophages (BMDM). Here, we show that after infection with a virulent strain of Mycobacterium tuberculosis (H37Rv), primary murine AM exhibit a unique transcriptomic signature characterized by metabolic reprogramming distinct from conventional BMDM. In contrast to BMDM, AM failed to shift from oxidative phosphorylation (OXPHOS) to glycolysis and consequently were unable to control infection with an avirulent strain (H37Ra). Importantly, healthy human AM infected with H37Ra equally demonstrated diminished energetics, recapitulating our observation in the murine model system. However, the results from seahorse showed that the shift towards glycolysis in both AM and BMDM was inhibited by H37Rv. We further demonstrated that pharmacological (e.g. metformin or the iron chelator desferrioxamine) reprogramming of AM towards glycolysis reduced necrosis and enhanced AM capacity to control H37Rv growth. Together, our results indicate that the unique bioenergetics of AM renders these cells a perfect target for Mtb survival and that metabolic reprogramming may be a viable host adjunctive therapy against TB.
2022-12-09 | GSE219072 | GEO
Project description:We found that mitochondrial oxidative phosphorylation (OXPHOS) plays a critical role in Th17 lineage specification. CD4 T cells differentiated under OXPHOS inhibited conditions show altered metabolic gene profiles (mitochondrial function, glycolysis, and TCA cycle) and pathways associated with cell proliferation. Furthermore, gene set enrichment analysis (GSEA) revealed that mitochondrial respiration impacts transcriptional profiles related to Th17 pathogenic signatures and BATF-sensitive gene clusters. Our study reveals a regulatory role of mitochondrial OXPHOS in transcriptional programming of Th17 lineage commitment.
2020-01-28 | GSE115282 | GEO
Project description:Our study showed that propranolol, carvedilol and nebivolol inhibited medulloblastoma cell proliferation and invasion by affecting energy metabolism pathways (OXPHOS and glycolysis) and by triggering a metabolic catastrophe that deprived tumor cells of their adaptive bioenergetics capacities. To better understand the importance of bioenergetics in response to treatment, we generated β-blocker-resistant ONS-76 cells by exposing them to increasing concentrations of propranolol, carvedilol or nebivolol for 16 weeks. The resulting cell lines i.e., ONS-76 RP, ONS-76 RC and ONS-76 RN, displayed a higher mitochondrial OCR and ATP production than the sensitive parental ONS-76 WT cells. By qRT-PCR, we showed that the expression of β-blockers canonical targets (β-ARs) was not altered in these resistant cells. Sequencing of total RNA from the four meduloblastoma cell models further indicated that cell resistance could not be explained by the down-regulation of key proteins of the β-AR downstream signaling, including the adenylate cyclase or their transcriptional targets. Our data also showed that the efficacy of propranolol, carvedilol and nebivolol was not impacted by β-AR silencing, further supporting the idea that β-blockers trigger an alternative signaling pathway in medulloblastoma cells.
2022-05-31 | GSE191165 | GEO
Project description:Our results revealed that among all 273 metabolites detected, the levels of metabolites involved in glucose-related glycolysis and gluconeogenesis were elevated in GCN2 deleted HSPCs. Moreover, GCN2 deletion specifically increased mitochondrial OXPHOS and suppressed anaerobic glycolysis in HSPCs.
2022-04-05 | ST002123 | MetabolomicsWorkbench
Project description:Human embryonic stem cells (hESCs) can self-renew infinitely, or differentiate into the three germ layer lineages in vitro with certain cues, holding great promise to model early human embryo development ex vivo.It is wildly accepted that hESCs take advantage of both glycolysis and mitochondrial respiration to favor the naïve pluripotency, while prefer glycolysis to support the primed pluripotency. Thus, the function of mitochondrial respiration in primed hESCs has been underestimated for a long time, and has not been fully understood yet. Herein, we report that the adenosine triphosphate (ATP) production rate is comparable between mitochondrial respiration and glycolysis, suggesting that mitoATP serves as one of the major sources of the ATP pool in primed hESCs. Next, we constructed a OGDH knockdown cell line whose ability of mitochondrial respiration was impired. Of note, OGDH deficiency led to the exit of primed pluripotency accompanied by cell death.Collectively, the current study unveils that OGDH acts as a key regulator to fine-tune the abundance of TCA cycle metabolites to ensure the mitochondrial respiration activity in primed hESCs, and highlights the pivotal roles of mitochondrial respiration in terms of ATP production and the maintenance of primed pluripotency.
2022-01-30 | GSE195539 | GEO
Project description:Heterotopic ossification (HO) is a non-physiological process of bone formation in which progenitor cells in soft tissues differentiate into chondrogenic cells. In the case of fibrodysplasia ossificans progressiva (FOP), a rare genetic disease characterized by progressive and systemic HO, the Activin A/mutated-ACVR1/mTORC1 cascade induces HO in progenitors, one of which is the fibro/adipogenic progenitors (FAPs) in muscle tissues. The relevant biological processes aberrantly regulated by activated mTORC1 remain unclear, however. RNA sequencing analyses revealed the enrichment of genes involved in oxidative phosphorylation (OXPHOS) during Activin A-induced chondrogenesis of mesenchymal stem cells derived from induced pluripotent stem cells (iPSCs) of FOP patients. Functional analyses showed a metabolic transition from glycolysis to OXPHOS during chondrogenesis, in conjunction with an upregulation of mitochondrial biogenesis. mTORC1 inhibition by rapamycin suppressed OXPHOS, and IACS-010759, an inhibitor of OXPHOS, inhibited cartilage matrix formation in vitro, indicating that OXPHOS is principally involved in mTORC1-induced chondrogenesis. Furthermore, IACS-010759 inhibited the muscle injury-induced enrichment of FAP genes and HO in transgenic mice carrying the mutated human ACVR1. These data indicated that OXPHOS is a critical downstream mediator of mTORC1 signaling in chondrogenesis and therefore is a potential FOP therapeutic target.
2024-02-16 | GSE221128 | GEO
Project description:Heterotopic ossification (HO) is a non-physiological process of bone formation in which progenitor cells in soft tissues differentiate into chondrogenic cells. In the case of fibrodysplasia ossificans progressiva (FOP), a rare genetic disease characterized by progressive and systemic HO, the Activin A/mutated-ACVR1/mTORC1 cascade induces HO in progenitors, one of which is the fibro/adipogenic progenitors (FAPs) in muscle tissues. The relevant biological processes aberrantly regulated by activated mTORC1 remain unclear, however. RNA sequencing analyses revealed the enrichment of genes involved in oxidative phosphorylation (OXPHOS) during Activin A-induced chondrogenesis of mesenchymal stem cells derived from induced pluripotent stem cells (iPSCs) of FOP patients. Functional analyses showed a metabolic transition from glycolysis to OXPHOS during chondrogenesis, in conjunction with an upregulation of mitochondrial biogenesis. mTORC1 inhibition by rapamycin suppressed OXPHOS, and IACS-010759, an inhibitor of OXPHOS, inhibited cartilage matrix formation in vitro, indicating that OXPHOS is principally involved in mTORC1-induced chondrogenesis. Furthermore, IACS-010759 inhibited the muscle injury-induced enrichment of FAP genes and HO in transgenic mice carrying the mutated human ACVR1. These data indicated that OXPHOS is a critical downstream mediator of mTORC1 signaling in chondrogenesis and therefore is a potential FOP therapeutic target.
2024-02-16 | GSE220725 | GEO
Project description:The current RNA sequencing and DNA methylation datasets provide an epigenomic map across the entire replicative lifespan of primary human fibroblast cell lines from n=6 healthy male and female donors and n=3 donors with lifespan-altering mitochondrial disease caused by mutations in the SURF1 gene. These datasets can be integrated with other measures collected in parallel along the lifespan, including cytological (cell size, morphology), bioenergetic (energy expenditure, derived ATP synthesis rates from Seahorse), secreted proteins, telomere length, and whole-genome sequencing (WGS) data. This dataset also includes experimental manipulations with treatments targeting oxidative phosphorylation (OXPHOS) and glycolysis, and glucocorticoid signaling, providing an opportunity to examine the influence of stress and bioenergetics on human aging biology. All processed data can be accessed and browsed at our webtool: https://columbia-picard.shinyapps.io/shinyapp-Lifespan_Study/
2021-11-12 | GSE179849 | GEO
Project description:In this study, we focused on demonstrating the metabolic aspect of NCoR1 in the regulation of dendritic cells (DCs) functionality. We report that NCoR1 deficient tolerogenic DCs meet their anabolic requirements through enhanced glycolysis and OxPhos, supported by FAO-driven oxygen consumption. Furthermore, individual and dual inhibition of glycolysis through HIF-1α inhibitor (KC7F2) and fatty acid oxidation through CPT1 inhibitor (etomoxir) significantly impaired the secretion of tolerogenic cytokines. To validate the same at the global mRNA level we did bulk RNA-seq to determine the differentially expressed genes in control and NCoR1 KD 6h CpG activated DCs with and without inhibitor treatment.
2024-01-01 | E-MTAB-12066 | biostudies-arrayexpress
Project description:Renal endothelial cells (RECs) from glomerular cortical and medullary kidney compartments are exposed to different microenvironmental conditions. Upon dehydration medullary RECs (mRECs) are exposed to extreme hyperosmolarity. However the heterogeneous phenotypes of RECs remain in-completely inventoried and how mRECs respond to dehydration is unknown. By single cell RNA-sequencing of >40000 RECs we identified 24 (including 8 novel) REC phenotypes highlighting extensive heterogeneity of RECs between and within the cortex glomeruli and medulla. In response to dehydration mRECs upregulated primarily the expression of genes involved in the hypoxia response glycolysis and surprisingly oxidative phosphorylation (OXPHOS). In vitro mRECs increased oxygen consumption in response to hyperosmolarity presumably to sustain ATP production for Na+/K+ ATPase pump-mediated salt excretion and to generate metabolic water during OXPHOS in order to counteract mREC hyperosmolarity unveiling a previously underappreciated role of OXPHOS. Overall RECs exhibit extensive heterogeneity and plasticity to adapt their metabolic transcriptome to overcome dehydration.
2019-12-12 | E-MTAB-8145 | biostudies-arrayexpress