Summary of Study ST004205
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
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 | ST004205 |
| Study Title | Lipidomic/Metabolomic Characterization of GPR34 KO, WT, TREM2 KO, and GPR34/TREM2 dKO iPSC1-derived microglia |
| Study Summary | GPR34 is a microglia-enriched receptor that senses cytotoxic lipids in Alzheimer’s disease and may interact with other lipid sensors like TREM2 to regulate metabolism. Using targeted lipid and metabolite profiling of iPSC-derived microglia with GPR34 KO, TREM2 KO, or GPR34/TREM2 double KO, we found that GPR34 deletion restores cholesterol metabolism defects in TREM2 KO cells and independently enhances fatty acid catabolism. |
| Institute | Denali Therapeutics |
| Last Name | Suh |
| First Name | Jung |
| Address | 161 Oyster Point Blvd |
| suh@dnli.com | |
| Phone | +1 6507973837 |
| Submit Date | 2025-09-05 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzML |
| Analysis Type Detail | LC-MS |
| Release Date | 2025-09-22 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| 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 |
Subject:
| Subject ID: | SU004357 |
| Subject Type: | Human |
| Subject Species: | Homo sapiens |
| Taxonomy ID: | 9606 |
Factors:
Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)
| mb_sample_id | local_sample_id | Genotype | Treatment | Sample source |
|---|---|---|---|---|
| SA484464 | HSA-000028167 | GPR34-KO | Myelin | iMicroglia |
| SA484465 | HSA-000028179 | GPR34-KO | Myelin | iMicroglia |
| SA484466 | HSA-000028155 | GPR34-KO | Myelin | iMicroglia |
| SA484467 | HSA-000028143 | GPR34-KO | Myelin | iMicroglia |
| SA484463 | HSA-000028166 | GPR34 KO | PBS | iMicroglia |
| SA484468 | HSA-000028154 | GPR34-KO | PBS | iMicroglia |
| SA484469 | HSA-000028142 | GPR34-KO | PBS | iMicroglia |
| SA484470 | HSA-000028178 | GPR34-KO | PBS | iMicroglia |
| SA484471 | HSA-000028149 | GPR34/TREM2-KO | Myelin | iMicroglia |
| SA484472 | HSA-000028185 | GPR34/TREM2-KO | Myelin | iMicroglia |
| SA484473 | HSA-000028173 | GPR34/TREM2-KO | Myelin | iMicroglia |
| SA484474 | HSA-000028161 | GPR34/TREM2-KO | Myelin | iMicroglia |
| SA484475 | HSA-000028160 | GPR34/TREM2-KO | PBS | iMicroglia |
| SA484476 | HSA-000028184 | GPR34/TREM2-KO | PBS | iMicroglia |
| SA484477 | HSA-000028172 | GPR34/TREM2-KO | PBS | iMicroglia |
| SA484478 | HSA-000028148 | GPR34/TREM2-KO | PBS | iMicroglia |
| SA484479 | HSA-000028402 | NA | NA | iMicroglia |
| SA484480 | HSA-000028403 | NA | NA | iMicroglia |
| SA484481 | HSA-000028400 | NA | NA | iMicroglia |
| SA484482 | HSA-000028401 | NA | NA | iMicroglia |
| SA484483 | HSA-000028158 | TREM2-KO | Myelin | iMicroglia |
| SA484484 | HSA-000028182 | TREM2-KO | Myelin | iMicroglia |
| SA484485 | HSA-000028170 | TREM2-KO | Myelin | iMicroglia |
| SA484486 | HSA-000028146 | TREM2-KO | Myelin | iMicroglia |
| SA484487 | HSA-000028169 | TREM2-KO | PBS | iMicroglia |
| SA484488 | HSA-000028181 | TREM2-KO | PBS | iMicroglia |
| SA484489 | HSA-000028145 | TREM2-KO | PBS | iMicroglia |
| SA484490 | HSA-000028157 | TREM2-KO | PBS | iMicroglia |
| SA484491 | HSA-000028176 | WT | Myelin | iMicroglia |
| SA484492 | HSA-000028164 | WT | Myelin | iMicroglia |
| SA484493 | HSA-000028140 | WT | Myelin | iMicroglia |
| SA484494 | HSA-000028152 | WT | Myelin | iMicroglia |
| SA484495 | HSA-000028151 | WT | PBS | iMicroglia |
| SA484496 | HSA-000028139 | WT | PBS | iMicroglia |
| SA484497 | HSA-000028175 | WT | PBS | iMicroglia |
| SA484498 | HSA-000028163 | WT | PBS | iMicroglia |
| Showing results 1 to 36 of 36 |
Collection:
| Collection ID: | CO004350 |
| Collection Summary: | iPSC1-derived microglia were harvested by aspirating medium then briefly washed with 1mL of ice-cold PBS solution and directly processed for lipidomic and metabolomic analysis. |
| Sample Type: | IPSC1-derived microglia |
| Storage Conditions: | -80℃ |
| Collection Vials: | Lobind 1.5 mL Eppendorf tubes |
| Storage Vials: | Lobind 1.5 mL Eppendorf tubes |
Treatment:
| Treatment ID: | TR004366 |
| Treatment Summary: | Demyelination is a key feature of neuronal degeneration in vivo in AD and amyloid mouse models (see Nugent et al. 2020, https://doi.org/10.1016/j.neuron.2019.12.007). For this reason, we selected it as a stimulus to evaluate microglial metabolism under a physiologically relevant stressor in vitro. Cells were treated for 48 hours with PBS or Myelin, followed by lipid extraction. |
Sample Preparation:
| Sampleprep ID: | SP004363 |
| Sampleprep Summary: | Cells were harvested by aspirating the medium, briefly washed with 1 mL of ice-cold PBS, and then lysed in 50 µL methanol containing stable-isotope internal standards. Samples were vortexed, adjusted to 100 µl with MS-grade H₂O, and transferred to 1.5 ml Protein LoBind tubes on ice. 100 µl of Methyl tert-butyl ether (MTBE)was added, vortexed and centrifuged at 21,000 g for 10 min at 4 °C. The two phases were separated: the top (non-polar lipids) and bottom (polar metabolites) were collected into glass vials, dried overnight in a Genevac EZ3, and resuspended in 100 µl of methanol (lipids) or 9:1 methanol:H₂O (metabolites) for LC-MS/MS analysis. |
| Processing Storage Conditions: | On ice |
| Extract Storage: | -20℃ |
Chromatography:
| Chromatography ID: | CH005308 |
| Instrument Name: | Agilent 1290 Infinity II |
| Column Name: | Waters ACQUITY UPLC BEH C18 (100 x 2.1mm,1.7um) |
| Column Temperature: | 55 |
| Flow Gradient: | 0.0-8.0 min from 45% B to 99% B, 8.0-9.0 min at 99% B, 9.0-9.1 min to 45% B, and 9.1-10.0 min at 45% B. |
| Flow Rate: | 0.25 mL/min |
| Sample Injection: | 5 |
| Solvent A: | 60% acetonitrile/40% water; 10 mM ammonium formate; 0.1% formic acid |
| Solvent B: | 90% isopropyl alcohol/10% acetonitrile; 10 mM ammonium formate; 0.1% formic acid |
| Chromatography Type: | Reversed phase |
| Chromatography ID: | CH005309 |
| Instrument Name: | Agilent 1290 Infinity II |
| Column Name: | Waters ACQUITY UPLC BEH C18 (100 x 2.1mm,1.7um) |
| Column Temperature: | 55 |
| Flow Gradient: | 0.0-8.0 min from 45% B to 99% B, 8.0-9.0 min at 99% B, 9.0-9.1 min to 45% B, and 9.1-10.0 min at 45% B. |
| Flow Rate: | 0.25 mL/min |
| Sample Injection: | 5 |
| Solvent A: | 60% acetonitrile/40% water; 10 mM ammonium acetate; 0.1% acetic acid |
| Solvent B: | 90% isopropyl alcohol/10% acetonitrile; 10 mM ammonium acetate; 0.1% acetic acid |
| Chromatography Type: | Reversed phase |
| Chromatography ID: | CH005310 |
| Instrument Name: | Agilent 1290 Infinity II |
| Column Name: | Waters ACQUITY UPLC BEH Amide (150 x 2.1mm,1.7um) |
| Column Temperature: | 55 |
| Flow Gradient: | 0.0-8.0 min from 45% B to 99% B, 8.0-9.0 min at 99% B, 9.0-9.1 min to 45% B, and 9.1-10.0 min at 45% B. |
| Flow Rate: | 0.25 mL/min |
| Sample Injection: | 8 |
| Solvent A: | 60% acetonitrile/40% water;10 mM ammonium formate; 0.1% formic acid |
| Solvent B: | 90% isopropyl alcohol/ 10% acetonitrile;10 mM ammonium formate; 0.1% formic acid |
| Chromatography Type: | HILIC |
Analysis:
| Analysis ID: | AN006992 |
| Analysis Type: | MS |
| Chromatography ID: | CH005308 |
| Num Factors: | 10 |
| Num Metabolites: | 140 |
| Units: | normalized peak area |
| Analysis ID: | AN006993 |
| Analysis Type: | MS |
| Chromatography ID: | CH005309 |
| Num Factors: | 10 |
| Num Metabolites: | 119 |
| Units: | normalized peak area |
| Analysis ID: | AN006994 |
| Analysis Type: | MS |
| Chromatography ID: | CH005310 |
| Num Factors: | 10 |
| Num Metabolites: | 216 |
| Units: | normalized peak area |
