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 |
Select appropriate tab below to view additional metadata details:
Combined analysis:
| Analysis ID | AN004002 |
|---|---|
| Analysis type | MS |
| Chromatography type | None (Direct infusion) |
| Chromatography system | none |
| Column | none |
| MS Type | MALDI |
| MS instrument type | QTOF |
| MS instrument name | Waters Synapt G2 XS QTOF |
| Ion Mode | NEGATIVE |
| Units | Intensity per pixel |
MS:
| MS ID: | MS003750 |
| Analysis ID: | AN004002 |
| Instrument Name: | Waters Synapt G2 XS QTOF |
| Instrument Type: | QTOF |
| MS Type: | MALDI |
| MS Comments: | For the detection of lipids, a Waters SynaptG2-Xs high-definition mass spectrometer equipped with traveling wave ion mobility was employed with the following parameters. The laser was operating at 2000 Hz with an energy of 300 AU and spot size of 50 μm at X and Y coordinates of 100μm with mass range set at 50 – 1000 m/z in negative mode. MALDI-MSI data files were processed to adjust for mass drift during the MALDI scan and to enhance image quality and improve signal-tonoise ratio using an algorithm available within the High-Definition Imaging (HDI) software (Waters Corp). To adjust for mass drift during the MALDI scan, raw files were processed using a carefully curated list of 20 MALDI NEDC matrix peaks (m/z), 26 small molecule MALDI peaks(m/z), and 24 lipid peaks(m/z). Files were processed at a sample duration of 10 sec at a frequency rate of 0.5 min, and an m/z window of 0.1 Da, using an internal lock mass of previously defined metabolite of taurine 124.007 m/z with a tolerance of 1amu and a minimum signal intensity of 100,000 counts. Data acquisition spectrums were uploaded to the HDI software for the generation of lipid images. Regions of interest (ROIs) were user defined by a blinded investigator using anatomical reference points based on the mouse Allen Brain atlas. For all pixels defined within a ROI, peak intensities were averaged and normalized by total ion current (TIC) and number of pixels. |
| Ion Mode: | NEGATIVE |
