Summary of Study ST002453
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 PR001580. The data can be accessed directly via it's Project DOI: 10.21228/M8G711 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 | ST002453 |
| Study Title | APOE modulates microglial immunometabolism in response to age, amyloid pathology, and inflammatory challenge (Part 3 of 3) |
| Study Summary | The E4 allele of Apolipoprotein E (APOE) is associated with both metabolic dysfunction and a heightened pro-inflammatory response – two findings that may be intrinsically linked through the concept of immunometabolism. Here, we combined bulk, single-cell, and spatial transcriptomics with cell-specific and spatially resolved metabolic analyses to systematically address the role of APOE across age, neuroinflammation, and AD pathology. RNAseq highlighted immunometabolic changes across the APOE4 glial transcriptome, specifically in subsets of metabolically distinct microglia enriched in the E4 brain during aging or following an inflammatory challenge. E4 microglia display increased Hif1α expression, a disrupted TCA cycle, and are inherently pro-glycolytic, while spatial transcriptomics and MALDI mass spectrometry imaging highlight an E4-specific response to amyloid that is characterized by widespread alterations in lipid metabolism. Taken together, our findings emphasize a central role for APOE in regulating microglial immunometabolism. |
| Institute | University of Kentucky |
| Department | Physiology |
| Laboratory | Lance Johnson; Josh Morganti |
| Last Name | Devanney |
| First Name | Nicholas |
| Address | Physiology, 760 Press Ave, Healthy Kentucky Research Bldg, Rm152, Lexington, Kentucky, 40508, USA |
| Nicholas.Devanney@uky.edu | |
| Phone | 8593238083 |
| Submit Date | 2022-11-14 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | raw(Waters) |
| Analysis Type Detail | MALDI-MS |
| Release Date | 2023-01-25 |
| Release Version | 1 |
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Sample Preparation:
| Sampleprep ID: | SP002548 |
| Sampleprep Summary: | Prepared brain hemispheres were cryosectioned to 10 μm thick coronal sections at approximately Bregma -2.00 mm. Brain sections were mounted on glass slides and prepared for MALDI MSI as follows: After desiccation for one hour, slides were sprayed with 14 passes of 7mg/mL N-(1-Naphthyl) ethylenediamine dihydrochloride (NEDC) matrix (Sigma) in 70% methanol (HPLC-grade, Sigma) which was applied at 0.06mL/min with a 3mm offset and a velocity of 1200mm/min at 30°C and 10psi using the M5 Sprayer with a heated tray of 50°C. Slides were used immediately or stored in a desiccator until analysis. |
