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
Email	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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Treatment:

Treatment ID:	TR002967
Treatment Summary:	Briefly, bone marrow cells were flushed from the tibia and femurs of 6- to 12-week-old male Apoe-/-, Apoe+/-, or wildtype mice on C57BL/6J background. Cells were cultured in complete media containing DMEM (Corning, USA) supplemented with 10% fetal bovine serum (GIBCO, USA), 1% GlutaMax (GIBCO, USA), and 1% penicillin-streptomycin (GIBCO, USA) and differentiated with 25 ng/ml mouse M-CSF (Peprotech, USA) for 6 days in 37C and 5% CO2. BMDM were then seeded into 12-well culture plates (Corning, USA) at a concentration of 3 x 10^5. Stimulation was done with 20 ng/mL IL-4 for 16 hours prior to collection.

Treatment ID:

TR002967

Treatment Summary:

Briefly, bone marrow cells were flushed from the tibia and femurs of 6- to 12-week-old male Apoe-/-, Apoe+/-, or wildtype mice on C57BL/6J background. Cells were cultured in complete media containing DMEM (Corning, USA) supplemented with 10% fetal bovine serum (GIBCO, USA), 1% GlutaMax (GIBCO, USA), and 1% penicillin-streptomycin (GIBCO, USA) and differentiated with 25 ng/ml mouse M-CSF (Peprotech, USA) for 6 days in 37C and 5% CO2. BMDM were then seeded into 12-well culture plates (Corning, USA) at a concentration of 3 x 10^5. Stimulation was done with 20 ng/mL IL-4 for 16 hours prior to collection.