Summary of project PR002651
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 PR002651. The data can be accessed directly via it's Project DOI: 10.21228/M8055H This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR002651 |
| Project DOI: | doi: 10.21228/M8055H |
| Project Title: | GPR34 regulates microglia state and loss-of-function rescues TREM2 metabolic dysfunction |
| Project Type: | cellular study |
| Project Summary: | Microglia are implicated in modifying neurodegenerative disease risk in the central nervous system (CNS). GPR34 is a microglia-enriched G-protein coupled receptor that detects cytotoxic lipids upregulated in Alzheimer’s Disease (AD). Since dysregulated lipid metabolism occurs in disease, we hypothesized GPR34 could act with other lipid sensors, such as TREM2, to regulate microglial function. Here, we report that GPR34 knockout (KO) rescues dysregulated cholesterol metabolism in TREM2 KO iPSC-derived microglia (iMG) and alone promotes fatty acid catabolism without the proton leak observed in TREM2 KO. Loss of GPR34 downregulated ERK signaling, while its agonism promoted interaction with and activation of ERK. In healthy and amyloid mouse models, Gpr34 KO accelerated the conversion of homeostatic microglia to disease-associated microglia (DAM) states. Additionally, in Gpr34 KO amyloid mouse brain, the frequency of large plaques was increased compared to WT, indicating that Gpr34 KO microglia may promote amyloid aggregation. Overall, our data suggest GPR34 as a therapeutic target for modulating microglial function to slow AD progression. |
| Institute: | Denali Therapeutics |
| Last Name: | Suh |
| First Name: | Jung |
| Address: | 161 Oyster Point Blvd, South San Francisco, California, 94080, USA |
| Email: | suh@dnli.com |
| Phone: | +1 6507973837 |
Summary of all studies in project PR002651
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST004205 | Lipidomic/Metabolomic Characterization of GPR34 KO, WT, TREM2 KO, and GPR34/TREM2 dKO iPSC1-derived microglia | Homo sapiens | Denali Therapeutics | MS | 2025-09-22 | 1 | 36 | Uploaded data (16.1M)* |
| ST004206 | Lipidomic Profiling of Sorted Microglia in GPR34-KO/APP-KI Mice Across 4, 8, 16, and 24 Months | Mus musculus | Denali Therapeutics | MS | 2025-09-22 | 1 | 138 | Uploaded data (21.4M)* |
