Summary of Study ST002846
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001781. The data can be accessed directly via it's Project DOI: 10.21228/M8H432 This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST002846 |
| Study Title | Apolipoprotein E suppresses hyperlipidemia-driven hematopoiesis & inflammation by controlling mitochondrial metabolism |
| Study Summary | Apolipoprotein E (ApoE) is recognized for its pleiotropic properties that suppress inflammation. We report that ApoE serves as a metabolic rheostat that regulates microRNA-control of glycolytic and mitochondrial activity in myeloid cells and hematopoietic stem & progenitor cells (HSPCs). ApoE expression in myeloid cells increases microRNA-146a, which reduces NF-κB-driven GLUT1 expression and glycolytic activity. In contrast, ApoE expression reduces microRNA-142a, which increases CPT1A expression, fatty acid oxidation, and oxidative phosphorylation. Improved mitochondrial metabolism by ApoE expression causes an enrichment of TCA cycle metabolites and NAD+ in macrophages. The study of mice with conditional ApoE expression supports the capacity for ApoE to foster microRNA-controlled immunometabolism. Modulation of microRNA-146a & -142a in the hematopoietic system of hyperlipidemic mice using RNA mimics & antagonists, respectively, improves mitochondrial metabolism, which suppresses inflammation and hematopoiesis. Our findings unveil an RNA regulatory network, controlled by ApoE, which exerts metabolic control over hematopoiesis and inflammation in hyperlipidemia. |
| Institute | Northwestern University |
| Last Name | Stoolman |
| First Name | Joshua |
| Address | 303 E Superior Street, Chicago, IL 60611 |
| joshua.stoolman@northwestern.edu | |
| Phone | 7343559440 |
| Submit Date | 2023-07-20 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | raw(Thermo) |
| Analysis Type Detail | LC-MS |
| Release Date | 2024-05-01 |
| Release Version | 1 |
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Collection:
| Collection ID: | CO002951 |
| Collection Summary: | BMDMs were seeded in a 6-well cell culture plate at a density of 50,000/well, and incubated in complete media at 37C & 5% CO2 overnight. Cells were gently washed 4x with DPBS before freezing at -80C. For metabolite extraction, cells were extracted with 1 mL HPLC-grade methanol/water 80:20. Cell lysates were centrifuged at 18,000 x g for 10 min. Supernatants were collected for downstream metabolomic analysis. The samples were evaporated using a stream of nitrogen. Subsequently metabolites were reconstituted in 50% acetonitrile in HPLC-grade water,vortexed and centrifuged to remove any debris. Samples were analyzed by Ultra-High-Performance Liquid Chromatography and High-Resolution Mass Spectrometry and Tandem Mass Spectrometry (UHPLC-MS/MS). Specifically, the system consisted of a Thermo Q-Exactive in line with an electrospray source and an Ultimate3000 (Thermo Fisher, USA) series HPLC consisting of a binary pump, degasser, and auto-sampler outfitted with an Xbridge Amide column (Waters; dimensions of 4.6mm × 100mm and a 3.5μm particle size). Mobile phase A contained 95% (vol/vol) water, 5% (vol/vol) acetonitrile, 10mM ammonium hydroxide, 10mM ammonium acetate, pH = 9.0; and mobile phase B was 100% Acetonitrile. The gradient was as follows: 0 min, 15% A; 2.5 min, 30% A; 7 min, 43% A; 16 min, 62% A; 16.1-18 min, 75% A; 18-25 min, 15% A with a flow rate of 400μL/min. The capillary of the ESI source was set to 275°C, with sheath gas at 45 arbitrary units, auxiliary gas at 5 arbitrary units, and the spray voltage at 4.0kV. In positive/negative polarity switching mode, an m/z scan automatic gain control (AGC) target was set at 1x106 and the maximum injection time was 200 ms. The top 5 precursor ions were subsequently fragmented, in a data-dependent manner, using the higher energy collisional dissociation (HCD) cell set to 30% normalized collision energy in MS2 at a resolution power of 17,500. |
| Sample Type: | Macrophages |
| Storage Conditions: | -80℃ |
