DNA methylation changes in regional lung macrophages are associated with metabolic differences
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA548341 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:A number of pulmonary diseases occur with upper lobe predominance, including cystic fibrosis and smoking-related chronic obstructive pulmonary disease. In the healthy lung, several physiologic and metabolic factors exhibit disparity when comparing the upper lobe of the lung to lower lobe, including differences in oxygenation, ventilation, lymphatic flow, pH, and blood flow. In this study, we asked whether these regional differences in the lung are associated with DNA methylation changes in lung macrophages that could potentially lead to altered cell responsiveness upon subsequent environmental challenge. All analyses were performed using primary lung macrophages collected via bronchoalveolar lavage from healthy human subjects with normal pulmonary function. Epigenome-wide DNA methylation was examined via Infinium MethylationEPIC (850K) array and validated by targeted next-generation bisulfite sequencing. We observed 95 CpG loci with significant differential methylation in lung macrophages, comparing upper lobe to lower lobe (all false discovery rate < 0.05). Several of these genes, including CLIP4, HSH2D, NR4A1, SNX10, and TYK2, have been implicated as participants in inflammatory/immune-related biological processes. Functionally, we identified phenotypic differences in oxygen use, comparing upper versus lower lung macrophages. Our results support a hypothesis that epigenetic changes, specifically DNA methylation, at a multitude of gene loci in lung macrophages are associated with metabolic differences regionally in lung.
| S-EPMC6686200 | biostudies-literature
Project description:A flexible fiberoptic bronchoscope was inserted trans-orally and advanced through the vocal cords of subjects. Brochoalveolar lavage (BAL) fluid was obtained from tertiary airways in the right upper and lower lobes. The BAL procedure was performed sequentially in the right upper lobe (RUL) and right lower lobe (RLL) with 20 ml of sterile saline followed by 10 ml of air and this was repeated for a total of 5 times per airway. BAL fluid was then filtered through 2-layer gauze, centrifuged, and washed twice in 0.9% NaCl. Cells were counted with a T10 automated cell counter. Cytospins were performed using a Shandon Cytospin 3 centrifuge. 75,000 cells resuspended in 200 l of 0.9% NaCl were loaded into a cytology funnel and centrifuged for 10 mins. Cells were allowed to air dry and processed for viewing via Hema 3 Stat pack. One pair of samples (GEO accessions GSM3610354 [H_1_RLL] and GSM3610362 [H_1_RUL]) from our previous publication, collected and measured in the same manner, was also included in our present analysis. DNA was extracted from lung macrophages via Qiagen DNeasy Blood and Tissue Kit. DNA was quantitated on a Qubit 3.0 Fluorometer. Bisulfite conversion of DNA was performed using the Zymo EZ DNA methylation kit. The Illumina MethylationEPIC array hybridization and scanning were performed at the University of Southern California Molecular Genomics Core.
2019-08-20 | GSE132547 | GEO
Project description:Background: Despite recent studies investigating the involvement of single cells in regional differences of the small intestine (SI), the metabolic contribution of the duodenum, jejunum, and ileum to the overall intestinal metabolism is still unclear. Basic procedures and main findings: Using an untargeted proteomics approach, we identified similarities and differences between the three intestinal tracts of C57BL/6J mice and found that proteins highly abundant in the mouse ileum correlated with high ileal expression of the corresponding genes in humans. Consistent with human data, we detected increasing abundance of lysosomal acid lipase (LAL) in C57BL/6J mice from the duodenum to ileum. LAL is the only enzyme known to degrade triacylglycerols and cholesteryl esters within the lysosome. Lipid accumulation in various organs along with gastrointestinal disturbances and malabsorption are typical features of patients and mice with LAL deficiency. We previously demonstrated that macrophages massively infiltrate the SI of Lal-deficient (KO) mice, especially the duodenum. To identify potential mechanisms behind the intestinal lipid accumulation and infiltration of immune cells, we used untargeted proteomics. Our results revealed a general inflammatory response and a common lipid-associated macrophage phenotype in all three intestinal segments of Lal KO mice, accompanied by higher expression of GPNMB and increased concentrations of circulating sTREM2. However, only duodenal macrophages activated a metabolic switch from lipids to other pathways such as glycolysis, TCA cycle, and oxidative phosphorylation to meet their high energy demand. Unexpectedly, these pathways were downregulated in the jejunum and ileum of Lal KO mice. Conclusion: Our results provide new insights into the process of absorption in control mice and the basis for novel markers of LAL-D and/or systemic inflammation in LAL-D.
2024-02-20 | PXD048378 | Pride
Project description:Background: Although chamber specialization is critical for proper cardiac function, a comprehensive, genome-wide analysis of the cardiac transcriptome, including identification of regional differences in mRNA and lncRNA expression patterns for the four chambers and interventricular septum of the non-failing human heart, has not been performed. Methods and Results: mRNA and long noncoding RNA (lncRNA) transcriptional profiling of the left (LA) and right (RA) atria, left (LV) and right (RV) ventricles, and the interventricular septum (IVS) of non-failing human hearts (N=8) was performed by deep sequencing. Analysis of the mRNA and lncRNA expression profiles revealed that the different regions of the heart are distinct. Differential expression analysis of paired tissue samples identified 5,747 mRNAs and 2,794 lncRNAs with chamber-enriched expression patterns. The largest differences in mRNA and lncRNA expression were evident between atria and ventricular samples, including regional differences in ~20% of all cardiac expressed mRNA and lncRNA transcripts. Regional differences in mRNA and lncRNA expression were also evident, although to a lesser extent, between the LA and RA, and between the LV, RV and IVS. Gene ontology classification of differentially expressed gene sets revealed regional differences in chamber specialization, including differences in signaling, metabolism, and muscle contraction. Sex differences in mRNA and lncRNA gene expression profiles were also identified between male and female LA and RA samples. Conclusions: There are marked regional differences in the mRNA and lncRNA expression profiles in non-failing adult human heart, and are associated with chamber specialization.
2018-10-16 | GSE112339 | GEO
Project description:Purpose: In the C57BL/6J mouse retina, hyperoxia-induced degeneration of photoreceptors shows strong regional variation, beginning at a locus ~0.5mm inferior to the optic disc. To identify gene expression differences that might underlie this variability in vulnerability, we have used microarray techniques to describe regional (superior-inferior) variations in gene expression in the retina.
2010-04-08 | GSE21246 | GEO
Project description:The role of shear stress, the frictional force of blood flow, on the endothelium has been well documented. Differences in shear stress can have profound effects on endothelial and blood vessel biology. Endothelial cells (ECs), termed endocardial ECs, line the heart chambers and are exposed to complex shear stress patterns. While it has been demonstrated that shear stress is important for heart development, little has been shown on the role of shear stress on adult ECs. 4D-MRI studies demonstrate regional differences in blood residence time. We sought to determine the effect of regional differences in endocardial shear stress on the endocardial transcriptome using RNA sequencing (RNA-seq) on 3 different regions (apex, mid-ventricle, outflow tract) from 8 adult pigs, for a total of 24 RNA-seq assays.
2015-12-31 | E-MTAB-3669 | biostudies-arrayexpress
Project description:Regional Differences in Progenitor Consumption Dynamics Shape Brain Growth during Development
| PRJNA1008340 | ENA
Project description:Purpose: In the C57BL/6J mouse retina, hyperoxia-induced degeneration of photoreceptors shows strong regional variation, beginning at a locus ~0.5mm inferior to the optic disc. To identify gene expression differences that might underlie this variability in vulnerability, we have used microarray techniques to describe regional (superior-inferior) variations in gene expression in the retina. Methods: Young adult C57BL/6J mice raised in dim cyclic illumination (12h 5lux, 12h darkness) were exposed to hyperoxia (75% oxygen for 2w). Retinas were collected from hyperoxia-exposed and control animals without fixation, and divided into superior and inferior halves. RNA was extracted from each sample, purified and hybridised to mouse 1.0 ST arrays (Affymetrix). The consistency of the microarray results was assessed with quantitative PCR for selected genes. Expression data were analysed to identify genes and ncRNAs whose differential expression between superior and inferior retina could be associated with relative vulnerability to hyperoxia.
2010-04-08 | E-GEOD-21246 | biostudies-arrayexpress
Project description:Thiele2013 - Lung macrophages
The model of lung macrophages metabolism is derived from the community-driven global reconstruction of human metabolism (version 2.02, MODEL1109130000
).
This model is described in the article:
A community-driven global reconstruction of human metabolism.
Thiele I, et al
.
Nature Biotechnology
Abstract:
Multiple models of human metabolism have been reconstructed, but each represents only a subset of our knowledge. Here we describe Recon 2, a community-driven,
consensus 'metabolic reconstruction', which is the most comprehensive representation of human metabolism that is applicable to computational modeling. Compared
with its predecessors, the reconstruction has improved topological and functional features, including ~2x more reactions and ~1.7x more unique metabolites. Using
Recon 2 we predicted changes in metabolite biomarkers for 49 inborn errors of metabolism with 77% accuracy when compared to experimental data. Mapping metabolomic
data and drug information onto Recon 2 demonstrates its potential for integrating and analyzing diverse data types. Using protein expression data, we automatically
generated a compendium of 65 cell type-specific models, providing a basis for manual curation or investigation of cell-specific metabolic properties. Recon 2 will
facilitate many future biomedical studies and is freely available at http://humanmetabolism.org/.
This model is hosted on BioModels Database
and identified by: MODEL1310110051
.
To cite BioModels Database, please use: BioModels Database: An enhanced,
curated and annotated resource for published quantitative kinetic models
.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer
to CC0 Public Domain Dedication
for more information.
2005-01-01 | MODEL1310110051 | BioModels
Project description:Microglia are the specialised macrophages of the central nervous system parenchyma. Diversity in macrophages is increasingly apparent in tissues outside the brain however understanding is negligible for microglia. In the present study, we present the first genome-wide analysis of microglia from discrete brain regions that reveals their multiple region-dependent transcriptional identities. Differences in bioenergetic and immunoregulatory pathways are the major sources of transcriptional heterogeneity. Region-specific differences in immunophenotype suggest cerebellar and hippocampal microglia exist in a more immune vigilant state, but distinct from the conventional M1/M2 paradigm of activation. Functional responses correlate with regional transcriptional immunophenotypes. We also show that region-dependent differences in microglial immunophenotype are superimposed upon a core profile distinguishing all microglia from systemic macrophages. We suggest microglial diversity may enable microglia to accomplish their wide-ranging homeostatic functions but could also underlie region-specific sensitivity to neuroinflammatory-mediated degeneration. During ageing key findings were made regarding the reinforcement of a specific cerebellar immunophenotype and a contrasting loss in the distinction of the phenotype of the hippocampus. The present dataset provide an extensive underpinning resource for future studies to further define how microglial diversity influences the healthy, ageing and diseased brain.
2015-10-01 | GSE62420 | GEO