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 |
Select appropriate tab below to view additional metadata details:
Combined analysis:
| Analysis ID | AN004664 |
|---|---|
| Analysis type | MS |
| Chromatography type | HILIC |
| Chromatography system | Thermo Fisher UltiMate 3000 |
| Column | Waters XBridge Amide (100 x 4.6mm, 3.5um) |
| MS Type | ESI |
| MS instrument type | Orbitrap |
| MS instrument name | Thermo Q Exactive Plus Orbitrap |
| Ion Mode | UNSPECIFIED |
| Units | Peak area |
MS:
| MS ID: | MS004411 |
| Analysis ID: | AN004664 |
| Instrument Name: | Thermo Q Exactive Plus Orbitrap |
| Instrument Type: | Orbitrap |
| MS Type: | ESI |
| MS Comments: | A 15μl aliquot of the sample was used for high-resolution HPLC-tandem mass spectrometry. High-resolution HPLC-tandem mass spectrometry was performed on a Q-Exactive (ThermoFisher Scientific) in line with an electrospray source and an UltiMate 3000 (ThermoFisher Scientific) series HPLC consisting of a binary pump, degasser and autosampler outfitted with a XBridge Amide column (Waters; 4.6 mm × 100 mm dimension and a 3.5 μm particle size). The capillary of the electrospray ionization source was set to 275 °C, with sheath gas at 45 arbitrary units, auxiliary gas at 5 arbitrary units and the spray voltage at 4.0 kV. A mass/charge ratio scan ranging from 70 to 850 was used in positive/negative polarity switching mode. MS1 data were collected at a resolution The automatic gain control (AGC) target was set at 1 × 106, with a maximum injection time of 200 ms. The top five precursor ions were fragmented using the higher-energy collisional dissociation cell with normalized collision energy of 30% in MS2 at a resolution of 17,500. Data were acquired with Xcalibur software (v.4.1; ThermoFisher Scientific). Analysis was performed using MeatboAnalyst (v5.0) with peak area normalized to total ion count for each sample. |
| Ion Mode: | UNSPECIFIED |
