Intracellular metabolic gradients dictate dependence on exogenous pyruvate
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE288364 | GEO | 2025/03/05
REPOSITORIES: GEO
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Project description:Intracellular metabolic gradients dictate dependence on exogenous pyruvate
| PRJNA1217024 | ENA
Project description:Pyruvate is a glycolytic metabolite used for energy production and macromolecule biosynthesis. However, little is known about its potential functions in tumorigenesis. Here,we report that exogenous pyruvate inhibits the proliferation of different types of cancer cells. This inhibitory effect of pyruvate on cell growth is attributed to its function as a signal molecule to repress histone gene expression, which leads to less compact chromatin structure and misregulation of genome-wide gene expression. Pyruvate represses histone gene expression by inducing the expression of NAD + biosynthesis enzyme, nicotinamide phosphoribosyltransferase (NAMPT), which increases NAD + levels and NAD + /NADH ratio. This increase activates the histone deacetylase activity of SIRT1. Chromatin immunoprecipitation analysis indicates that pyruvate enhances SIRT1 binding at histone gene promoters where it reduces histone acetylation. Although pyruvate delays cell entry into S phase, pyruvate represses histone gene expression independent of cell cycle progression. Moreover, we find that administration of pyruvate significantly reduces histone expression and retards tumor growth in xenograft mice without significant side effects. Using tissues from cervical cancer patients, we find intracellular pyruvate concentrations inversely correlate with histone protein levels. Together, we uncover a previously unknown function of pyruvate in histone gene expression and characterize pyruvate as a potential anti-cancer agent.
2019-12-05 | GSE135831 | GEO
Project description:The ground state of pluripotency is defined as a basal proliferative state free of epigenetic restriction, represented by mouse embryonic stem cells (ESCs) cultured with two kinase inhibitors (so-called “2i”). Through comparison with serum-grown ESCs, we identify epigenetic features characterizing 2i ESCs by proteome profiling of chromatin including post-translational histone modifications. The most prominent difference is H3K27me3 and its enzymatic writer complex PRC2 that are highly abundant on eu- and heterochromatin in 2i ESCs, with H3K27me3 redistributing outside canonical PRC2 targets in a CpG-dependent fashion. Using PRC2-deficient 2i ESCs, we identify epigenetic crosstalk with H3K27me3, including significant increases in H4 acetylation and DNA methylation. This suggests that the unique H3K27me3 configuration protects 2i ESCs from preparation to lineage priming. Interestingly, removal of DNA methylation in PRC2-deficient 2i ESCs lacking H3K27me3 using 5-azacytidine hardly affected ESC viability and transcriptome, showing that ESCs are independent of both major repressive epigenetic marks.
2018-11-21 | PXD007154 | Pride
Project description:We report that ES cells cultured in ground state (2i and 2i/LIF) culture conditions are heterogeneous and show heterogeneus expression of extraembryonic markers. Using a highly sensitive reporter for the endoderm marker Hex we can sort Hex high and low populations from either serum/LIF or 2i/LIF and demonstrate that they have different functional properties. Here we explored the transcriptional basis of these functional differences and noted that Hex low (HV-) and Hex high (HV+) populations showed more distinct expression profiles in 2i/LIF than in serum/LIF. Additionally in 2i/LIF the HV+ population showed an upregulation of extraembryonic markers (such as trophoblast stem cell specific genes) and also imprinted genes compared to the HV- population, which is not observed when these populations are sorted from serum/LIF. We also analysed the transcriptional effect of LIF in 2i by analysing unsorted ES cells cultured in either 2i alone or 2i with LIF. We observed that the addition of LIF led to an upregulation of extraembryonic markers but did not effect the expression of pluripotency genes, other than Klf4. Additionally, the most significantly upregulated genes from 2i/LIF cultured ES cells compared to 2i cultured ES cells showed the greatest correlation to placental tissue when compared to the GNF tissue specific expression database. This analysis, alongside functional experiments, suggested that HV+ ES cells in 2i/LIF corresponded to an extraembryonically primed population of cells and that the addition of LIF supported this population.
2013-06-11 | GSE45182 | GEO
Project description:BackgroundAnnually reoccurring microbial populations with strong spatial and temporal variations have been identified in estuarine environments, especially in those with long residence time such as the Chesapeake Bay (CB). However, it is unclear how microbial taxa cooccurr and how the inter-taxa networks respond to the strong environmental gradients in the estuaries.ResultsHere, we constructed co-occurrence networks on prokaryotic microbial communities in the CB, which included seasonal samples from seven spatial stations along the salinity gradients for three consecutive years. Our results showed that spatiotemporal variations of planktonic microbiomes promoted differentiations of the characteristics and stability of prokaryotic microbial networks in the CB estuary. Prokaryotic microbial networks exhibited a clear seasonal pattern where microbes were more closely connected during warm season compared to the associations during cold season. In addition, microbial networks were more stable in the lower Bay (ocean side) than those in the upper Bay (freshwater side). Multivariate regression tree (MRT) analysis and piecewise structural equation modeling (SEM) indicated that temperature, salinity and total suspended substances along with nutrient availability, particulate carbon and Chl a, affected the distribution and co-occurrence of microbial groups, such as Actinobacteria, Bacteroidetes, Cyanobacteria, Planctomycetes, Proteobacteria, and Verrucomicrobia. Interestingly, compared to the abundant groups (such as SAR11, Saprospiraceae and Actinomarinaceae), the rare taxa including OM60 (NOR5) clade (Gammaproteobacteria), Micrococcales (Actinobacteria), and NS11-12 marine group (Bacteroidetes) contributed greatly to the stability of microbial co-occurrence in the Bay. Modularity and cluster structures of microbial networks varied spatiotemporally, which provided valuable insights into the 'small world' (a group of more interconnected species), network stability, and habitat partitioning/preferences.ConclusionOur results shed light on how estuarine gradients alter the spatiotemporal variations of prokaryotic microbial networks in the estuarine ecosystem, as well as their adaptability to environmental disturbances and co-occurrence network complexity and stability.
| S-EPMC8627074 | biostudies-literature
Project description:Plants have long been thought to be less dependent on pollinators for seed production at higher elevations due to adverse pollination environments. However, recent research has yet to consistently support the generality of this expectation. In this study, we asked whether pollinator dependence decreases along an elevational gradient and how it varies with various reproductive traits. To answer these questions, we quantified pollinator-plant associations and various reproductive traits for 112 flowering plants spanning a large elevational gradient (990-4260 m a.s.l.) in the Qinghai-Tibet Plateau. We found that flowering plants in the Qinghai-Tibet Plateau region are highly dependent on pollinators for seed production (76.2% of seed production was contributed by animal pollinators and 44.6% of plants would produce no seed without pollinator visitation). Contrary to our expectation, there was no significant elevational gradient in pollinator dependence index. Although the pollinator dependence index was not significantly correlated with pollen limitation, flower size, floral longevity, or reward type, it was correlated with compatibility status and flowering time. These findings indicate that pollinator dependence does not decrease along an elevational gradient in the Qinghai-Tibet Plateau. Our study also highlights the severe vulnerability of flowering plant seed production to pollinator declines under global change in the Qinghai-Tibet Plateau region, particularly for early-flowering or self-incompatible plants growing at higher elevations (e.g., subnival belt).
| S-EPMC10435910 | biostudies-literature
Project description:This study describes the transcriptome profiling of: 1) Mof fl/fl mESCs cultured in 2i/LIF medium with Ethanol (WT) or 4-OHT (Mof-/-); 2) E14 mESCs cultured in 2i/LIF medium treated with H2O (control) or Etomoxir treatment (ETO, FAO inhibition) and ETO-released (Released).
2020-07-02 | GSE137138 | GEO
Project description:We report that ES cells cultured in ground state (2i and 2i/LIF) culture conditions are heterogeneous and show heterogeneus expression of extraembryonic markers. Using a highly sensitive reporter for the endoderm marker Hex we can sort Hex high and low populations from either serum/LIF or 2i/LIF and demonstrate that they have different functional properties. Here we explored the transcriptional basis of these functional differences and noted that Hex low (HV-) and Hex high (HV+) populations showed more distinct expression profiles in 2i/LIF than in serum/LIF. Additionally in 2i/LIF the HV+ population showed an upregulation of extraembryonic markers (such as trophoblast stem cell specific genes) and also imprinted genes compared to the HV- population, which is not observed when these populations are sorted from serum/LIF. We also analysed the transcriptional effect of LIF in 2i by analysing unsorted ES cells cultured in either 2i alone or 2i with LIF. We observed that the addition of LIF led to an upregulation of extraembryonic markers but did not effect the expression of pluripotency genes, other than Klf4. Additionally, the most significantly upregulated genes from 2i/LIF cultured ES cells compared to 2i cultured ES cells showed the greatest correlation to placental tissue when compared to the GNF tissue specific expression database. This analysis, alongside functional experiments, suggested that HV+ ES cells in 2i/LIF corresponded to an extraembryonically primed population of cells and that the addition of LIF supported this population. RNA-seq of sorted Hex low and high expressing ES cell populations cultured in serum/LIF or 2i/LIF as well as unsorted ES cells from 2i or 2i/LIF.
2013-06-11 | E-GEOD-45182 | biostudies-arrayexpress
Project description:BackgroundUnderstanding the drivers of large-scale vegetation change is critical to managing landscapes and key to predicting how projected climate and land use changes will affect regional vegetation patterns. This study aimed to improve our understanding of the role, magnitude and spatial distribution of the key environmental factors driving vegetation change in southern African savanna, and how they vary across physiographic gradients.Methodology/principal findingsWe applied Dynamic Factor Analysis (DFA), a multivariate times series dimension reduction technique to ten years of monthly remote sensing data (MODIS-derived normalized difference vegetation index, NDVI) and a suite of environmental covariates: precipitation, mean and maximum temperature, soil moisture, relative humidity, fire and potential evapotranspiration. Monthly NDVI was described by cyclic seasonal variation with distinct spatiotemporal patterns in different physiographic regions. Results support existing work emphasizing the importance of precipitation, soil moisture and fire on NDVI, but also reveal overlooked effects of temperature and evapotranspiration, particularly in regions with higher mean annual precipitation. Critically, spatial distributions of the weights of environmental covariates point to a transition in the importance of precipitation and soil moisture (strongest in grass-dominated regions with precipitation<750 mm) to fire, potential evapotranspiration, and temperature (strongest in tree-dominated regions with precipitation>950 mm).Conclusions/significanceWe quantified the combined spatiotemporal effects of an available suite of environmental drivers on NDVI across a large and diverse savanna region. The analysis supports known drivers of savanna vegetation but also uncovers important roles of temperature and evapotranspiration. Results highlight the utility of applying the DFA approach to remote sensing products for regional analyses of landscape change in the context of global environmental change. With the dramatic increase in global change research, this methodology augurs well for further development and application of spatially explicit time series modeling to studies at the intersection of ecology and remote sensing.
| S-EPMC3758306 | biostudies-literature
Project description:lncRNA profiles of ground state mouse embryonic stem cells cultured in 2i condition.
2017-12-30 | GSE87632 | GEO