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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Collection:
| Collection ID: | CO002535 |
| Collection Summary: | Three different mice for each experimental group (18 mice in total) were anesthetized via 5.0% isoflurane before exsanguination and transcardial perfusion with ice-cold Dulbecco’s phosphate buffered saline (DPBS; Gibco # 14040133). Following perfusion, hemibrains were quickly removed, leaving behind brainstem and cerebellum. Hemibrains were immediately placed in OCT compound (Fisher HealthCare Tissue Plus O.C.T. Compound Clear 4585) and gently lowered into isopentane (Sigma-Aldrich 2- Methylbutane M32631) in a beaker surrounded by dry ice (isopentane chilled to approximately -70°C). Hemibrains were submerged for 60 seconds, placed on dry ice, wrapped in aluminum foil, and stored at -80°C until sectioning. |
| Sample Type: | Brain |
