Explore the gene sets modulated by alterations in lactate levels.
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE246022 | GEO | 2024/07/03
REPOSITORIES: GEO
Similar Datasets
Project description:Purpose: Although glycolysis-derived lactate and bacterial product IPA are active metabolites, there is still a lack of understanding of their influence on metabolic and epigentic status of T cells. The aim of this study was to shed light on possible effects of lactate and IPA on function of T cells, including production of cytokines and regulation of trenscriptional factors. Method: Naive mice (8-12-week-old female mice) were sacrificed and CD4+ T cells were purified from spleens and lymph nodes. T lymphocytes were then treated with lactate or IPA for two days. To ensure that gene signatures were derived from T cells and not from contaminating APCs or B cells, T cell isolation kit from Miltenyi Biotec was used (purity over 95 %). Results: The analysis of differential expressed genes of lactate- and IPA-treated Th17 cells revealed multiple effects of extracellular lactate and bacterial IPA on the transcriptional profiles. Lactate induced expression of diverse genes associated with transcriptional signature of regulatory T cells. Conclusion: This study demonstrated that extracellular lactate and microbial metabolite IPA influence transcriptional programs in murine Th17 cells.
2022-11-25 | GSE193358 | GEO
Project description:On a daily basis, we turnover billions of apoptotic cells that are removed by professional and non-professional phagocytes1-10. While characterizing the transcriptional program of phagocytes, we discovered a novel solute carrier family (SLC) gene signature (33 SLC members) that is specifically modified during engulfment of apoptotic cells (efferocytosis) but not during antibody-mediated phagocytosis. When we assessed the functional relevance of these SLCs, we noted robust induction of an aerobic glycolysis program in engulfing phagocytes, initiated by SLC2A1-mediated glucose uptake, and suppression of oxidative phosphorylation program. Interestingly, the different steps of phagocytosis10,11, i.e. smell (‘find-me’ signals / sensing factors released by apoptotic cells), taste (phagocyte- apoptotic cell contact), and ingestion (corpse internalization), activated different molecules to promote this glycolytic process. Further, lactate, a natural by-product of aerobic glycolysis12,13, was released from engulfing phagocytes via SLC16A1, an SLC member activated after corpse uptake. While glycolysis within phagocytes contributed to actin polymerization and the continued uptake of corpses, the lactate released via SLC16A1 influenced the establishment of an anti-inflammatory environment. Collectively, these data reveal a novel SLC program activated during efferocytosis, identify a previously unknown reliance on aerobic glycolysis during apoptotic cell uptake, and that glycolytic byproducts of efferocytosis can also influence other cells in the microenvironment.
2018-11-30 | GSE119273 | GEO
Project description:Data files for manuscript "Lactate homeostasis is maintained through regulation of glycolysis and lipolysis"
2024-11-01 | MSV000096276 | MassIVE
Project description:Mammalian retinal metabolism favors aerobic glycolysis. However, the role of glycolytic metabolism in retinal morphogenesis remains unknown. We report that aerobic glycolysis is necessary for the early stages of retinal development. Taking advantage of an unbiased approach that combines the use of eye organoids and single-cell RNA sequencing, we identify specific glucose transporters and glycolytic genes in retinal progenitors. Next, we determine that the optic vesicle territory of mouse embryos displays elevated levels of glycolytic activity. At the functional level, we show that removal of Glucose transporter 1 and Lactate dehydrogenase A gene activity from developing retinal progenitors arrests eye morphogenesis. Surprisingly, we uncover that lactate-mediated upregulation of key eye-field transcription factors is controlled by the epigenetic modification of histone H3 acetylation through histone deacetylase activity. Our results identify an unexpected bioenergetic independent role of lactate as a signaling molecule necessary for mammalian eye morphogenesis.
2023-06-08 | GSE202758 | GEO
Project description:Mammalian retinal metabolism favors aerobic glycolysis. However, the role of glycolytic metabolism in retinal morphogenesis remains unknown. We report that aerobic glycolysis is necessary for the early stages of retinal development. Taking advantage of an unbiased approach that combines the use of eye organoids and single-cell RNA sequencing, we identify specific glucose transporters and glycolytic genes in retinal progenitors. Next, we determine that the optic vesicle territory of mouse embryos displays elevated levels of glycolytic activity. At the functional level, we show that removal of Glucose transporter 1 and Lactate dehydrogenase A gene activity from developing retinal progenitors arrests eye morphogenesis. Surprisingly, we uncover that lactate-mediated upregulation of key eye-field transcription factors is controlled by the epigenetic modification of histone H3 acetylation through histone deacetylase activity. Our results identify an unexpected bioenergetic independent role of lactate as a signaling molecule necessary for mammalian eye morphogenesis.
2023-06-08 | GSE202757 | GEO
Project description:Mammalian retinal metabolism favors aerobic glycolysis. However, the role of glycolytic metabolism in retinal morphogenesis remains unknown. We report that aerobic glycolysis is necessary for the early stages of retinal development. Taking advantage of an unbiased approach that combines the use of eye organoids and single-cell RNA sequencing, we identify specific glucose transporters and glycolytic genes in retinal progenitors. Next, we determine that the optic vesicle territory of mouse embryos displays elevated levels of glycolytic activity. At the functional level, we show that removal of Glucose transporter 1 and Lactate dehydrogenase A gene activity from developing retinal progenitors arrests eye morphogenesis. Surprisingly, we uncover that lactate-mediated upregulation of key eye-field transcription factors is controlled by the epigenetic modification of histone H3 acetylation through histone deacetylase activity. Our results identify an unexpected bioenergetic independent role of lactate as a signaling molecule necessary for mammalian eye morphogenesis.
2023-06-08 | GSE224648 | GEO
Project description:Histone acetylation involves the transfer of a two-carbon unit to nucleus as embedded in low-concentration metabolites. We find that lactate, a high-concentration metabolic by-product, can be a major carbon source for histone acetylation, through oxidation-dependent metabolism. Both in cells and in purified nucleus, 13C3-lactate carbons are incorporated into histone H4 (maximum incorporation: ~60%). In purified nucleus, this process depends on nucleus-localized lactate dehydrogenase (LDHA), the knockout of which abrogates the incorporation. Heterologous expression of nucleus-localized LDHA rescues the KO effect. Lactate itself increases histone acetylation, whereas inhibition of LDHA reduces the acetylation. In vitro and in vivo settings exhibit different lactate incorporation patterns, suggesting an influence of the microenvironment. Higher nuclear LDHA localization is observed in pancreatic cancer than in normal tissues, showing the disease relevance. Overall, lactate and nuclear LDHA can be major structural and regulatory players in the metabolism-epigenetics axis controlled by cell’s own or environmental status.
2023-11-21 | GSE235471 | GEO
Project description:L. plantarum is known to possess an L-lactate inducible lactate racemase activity (Goffin et al. 2005. J. Bacteriol. 187:6750). In the present study, microarrays were used in order to identify all genes that are up-regulated by L-lactate, but not by a racemic mixture of D- and L-lactate. A mutant of L. plantarum NCIMB8826 deficient for NAD-dependent L-lactate activity (TF101; Ferain et al. 1994. 176:596), and thus producing no L-lactate, was grown in MRS medium at 28°C until mid-exponential phase (OD600nm 0.75). The culture was then divided into 3 sub-cultures. Optically pure sodium L-lactate (200 mM) was added to the first sub-culture (TF101 + L-lac 200 mM). An equimolar mixture of sodium D- and L-lactate (100 mM each) was added to the second sub-culture (TF101 + L/D-lac 200 mM). The third sub-culture was not treated (TF101; reference sample). The three sub-cultures were further incubated at 28°C for 1h30 (a time known to be sufficient for induction of lactate racemase activity by L-lactate). Cells were harvested by centrifugation. Microarray data were used ot identify genes that are specifically induced by L-lactate (comparison of TF101 with TF101 + L-lac 200 mM), but not by DL-lactate (comparison of TF101 with T101 + L/D-lac 200 mM). There are no biological replicates.
2013-07-01 | E-GEOD-43518 | biostudies-arrayexpress
Project description:Lactate is abundant in the tumor environment as the secreted product of fermentative cells. In prostate cancer (PCa), cancer-associated fibroblasts are the major contributors and this secreted lactate is uptaken by cancer cells to sustain their mitochondrial metabolism. However, how lactate controls the metabolic and transcriptional regulation in tumors is far to be elucidated. Here, we identify an innovative lactate-driven mechanism able to increase the expression of genes involved in lipid metabolism in PCa cells. This regulation enhances intracellular lipid accumulation in lipid droplets (LDs) and provides acetyl moieties for histone acetylation, establishing a regulatory loop between metabolites and epigenetic control. Interestingly, inhibition of this loop by targeting bromodomains histone acetylation readers suppresses the expression of perilipin-2 (PLIN2), a crucial component of LDs, disrupting the lactate-dependent lipid metabolic rewiring. Since this metabolic-epigenetic regulatory loop sustains PCa metastatic potential, its targeting is of clinical relevance as demonstrated by the inhibition of PCa invasive potential in vivo. Overall, our findings show that lactate has both a metabolic and an epigenetic role in promoting PCa progression.
2022-01-31 | GSE195639 | GEO
Project description:Wounds, especially non healing wounds are characterised by elevated tissue lactate concentrations. Lactate is known for being able to stimulate collagen synthesis and vessel growth. Lately it has been shown that lactate, in vivo, plays an important role in homing of stem cells. With this work we aimed to show the influence of lactate on the gene expressionprofil of human mesenchymal stem cells (hMSC). hMSCs were obtained from bone marrow and characterised with fluorescence-activated cell sorting (FACS) analysis. Subsequently the hMSCs were treated with either 0, 5, 10 and 15 mM lactate (pH 7,4) for 24 hours. RNA Isolation from stimulated hMSCs and controls was performed. The Microarray analysis was performed using Affymetrix HuGene 1.0 ST Gene Chip. Selected targets were subsequently analysed using quantitative real time PCR (RTq-PCR). We were able to show that lactate in moderate concentrations of 5 respectively 10 mM leads to an anti-imflammatory, anti-apoptotic but growth and proliferation promoting gene expression after 24 h. In contrast, high latate concentrations of 15 mM leads to the opposed effect, namely promoting inflammation and apoptosis. Hypoxia induced genes did not not show any significant regulation. Contrary to expectation, we were not able to show any significant regulation of glycolysis associate candiadtes. We were able to show that lactate alters gene expression but does not change the cell phenotype, which might be helpful for further investigations of new treatment strategies for chronic non-healing wounds as well as tumor-therapy and neuronal plasticity. Timecourse experiment with hMSCs treated with 5, 10, 15 mM lactic acid for 1, 3, 7 days. hMSCs without lactate served as controls *** CEL files lost due to hard disk crash
2013-01-09 | E-GEOD-40205 | biostudies-arrayexpress