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 |
Chromatography:
| Chromatography ID: | CH003510 |
| Chromatography Summary: | Samples were analyzed by high-performance LC (HPLC) and high-resolution MS and MS/MS (HPLC-MS/MS). The system consists of Thermo Q Exactive with an electrospray source and an UltiMate3000 (Thermo Fisher Scientific) series HPLC consisting of a binary pump, degasser, and autosampler outfitted with an XBridge Amide column (Waters; dimensions of 4.6 mm by 100 mm and a 3.5-μm particle size). Mobile phase A contained water and acetonitrile (95/5, v/v), 10 mM ammonium hydroxide and 10 mM ammonium acetate (pH 9.0). Mobile phase B was 100% acetonitrile. The gradient was set to 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 400 μl min–1. |
| Instrument Name: | Thermo Fisher UltiMate 3000 |
| Column Name: | Waters XBridge Amide (100 x 4.6mm, 3.5um) |
| Column Temperature: | 275 |
| Flow Gradient: | 0 min, 15% A; 2.5 min, 30% A; 7 min, 43% A; 16 min, 62% A; 16.1 to 18 min, 75% A; and 18 to 25 min, 15% A |
| Flow Rate: | 400 μl/min |
| Solvent A: | 95% water/5% acetonitrile; 10 mM ammonium hydroxide; 10 mM ammonium acetate (pH 9.0) |
| Solvent B: | 100% acetonitrile |
| Chromatography Type: | HILIC |
