Summary of Study ST004206
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 | ST004206 |
| Study Title | Lipidomic Profiling of Sorted Microglia in GPR34-KO/APP-KI Mice Across 4, 8, 16, and 24 Months |
| Study Summary | GPR34 is a microglia-enriched receptor that senses cytotoxic lipids in Alzheimer’s disease. Targeted lipid profiling was performed on microglia sorted from GPR34 knockout and WT mice crossed with an amyloid precursor protein knock-in (APP-KI) Alzheimer’s disease model. Analyses at 4, 8, 16 and 24 months of age were used to assess the impact of GPR34 loss in vivo. |
| Institute | Denali Therapeutics |
| Last Name | Suh |
| First Name | Jung |
| Address | 161 Oyster Point Blvd |
| suh@dnli.com | |
| Phone | +1 6507973837 |
| Submit Date | 2025-09-15 |
| 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: | SU004358 |
| Subject Type: | Mammal |
| Subject Species: | Mus musculus |
| Taxonomy ID: | 10090 |
Factors:
Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)
| mb_sample_id | local_sample_id | Genotype | Disease_State | Age_months | Sample source |
|---|---|---|---|---|---|
| SA484499 | HSA-000030099 | GPR34-KO | APP-KI | 16 months | Microglia |
| SA484500 | HSA-000030100 | GPR34-KO | APP-KI | 16 months | Microglia |
| SA484501 | HSA-000030088 | GPR34-KO | APP-KI | 16 months | Microglia |
| SA484502 | HSA-000030101 | GPR34-KO | APP-KI | 16 months | Microglia |
| SA484503 | HSA-000030087 | GPR34-KO | APP-KI | 16 months | Microglia |
| SA484504 | HSA-000030089 | GPR34-KO | APP-KI | 16 months | Microglia |
| SA484505 | HSA-000035578 | GPR34-KO | APP-KI | 24 months | Microglia |
| SA484506 | HSA-000036513 | GPR34-KO | APP-KI | 24 months | Microglia |
| SA484507 | HSA-000035582 | GPR34-KO | APP-KI | 24 months | Microglia |
| SA484508 | HSA-000035577 | GPR34-KO | APP-KI | 24 months | Microglia |
| SA484509 | HSA-000035581 | GPR34-KO | APP-KI | 24 months | Microglia |
| SA484510 | HSA-000035580 | GPR34-KO | APP-KI | 24 months | Microglia |
| SA484511 | HSA-000035579 | GPR34-KO | APP-KI | 24 months | Microglia |
| SA484512 | HSA-000036512 | GPR34-KO | APP-KI | 24 months | Microglia |
| SA484513 | HSA-000035584 | GPR34-KO | APP-KI | 24 months | Microglia |
| SA484514 | HSA-000035583 | GPR34-KO | APP-KI | 24 months | Microglia |
| SA484515 | HSA-000036514 | GPR34-KO | APP-KI | 24 months | Microglia |
| SA484516 | HSA-000035576 | GPR34-KO | APP-KI | 24 months | Microglia |
| SA484517 | HSA-000018523 | GPR34-KO | APP-KI | 4 months | Microglia |
| SA484518 | HSA-000018531 | GPR34-KO | APP-KI | 4 months | Microglia |
| SA484519 | HSA-000018543 | GPR34-KO | APP-KI | 4 months | Microglia |
| SA484520 | HSA-000018547 | GPR34-KO | APP-KI | 4 months | Microglia |
| SA484521 | HSA-000018519 | GPR34-KO | APP-KI | 4 months | Microglia |
| SA484522 | HSA-000018535 | GPR34-KO | APP-KI | 4 months | Microglia |
| SA484523 | HSA-000018511 | GPR34-KO | APP-KI | 4 months | Microglia |
| SA484524 | HSA-000018515 | GPR34-KO | APP-KI | 4 months | Microglia |
| SA484525 | HSA-000018527 | GPR34-KO | APP-KI | 4 months | Microglia |
| SA484526 | HSA-000018539 | GPR34-KO | APP-KI | 4 months | Microglia |
| SA484527 | HSA-000023441 | GPR34-KO | APP-KI | 8 months | Microglia |
| SA484528 | HSA-000023433 | GPR34-KO | APP-KI | 8 months | Microglia |
| SA484529 | HSA-000023437 | GPR34-KO | APP-KI | 8 months | Microglia |
| SA484530 | HSA-000023425 | GPR34-KO | APP-KI | 8 months | Microglia |
| SA484531 | HSA-000023417 | GPR34-KO | APP-KI | 8 months | Microglia |
| SA484532 | HSA-000023449 | GPR34-KO | APP-KI | 8 months | Microglia |
| SA484533 | HSA-000023429 | GPR34-KO | APP-KI | 8 months | Microglia |
| SA484534 | HSA-000023445 | GPR34-KO | APP-KI | 8 months | Microglia |
| SA484535 | HSA-000023413 | GPR34-KO | APP-KI | 8 months | Microglia |
| SA484536 | HSA-000023421 | GPR34-KO | APP-KI | 8 months | Microglia |
| SA484537 | HSA-000030082 | GPR34-KO | WT | 16 months | Microglia |
| SA484538 | HSA-000030083 | GPR34-KO | WT | 16 months | Microglia |
| SA484539 | HSA-000030081 | GPR34-KO | WT | 16 months | Microglia |
| SA484540 | HSA-000030094 | GPR34-KO | WT | 16 months | Microglia |
| SA484541 | HSA-000030095 | GPR34-KO | WT | 16 months | Microglia |
| SA484542 | HSA-000030093 | GPR34-KO | WT | 16 months | Microglia |
| SA484543 | HSA-000018522 | GPR34-KO | WT | 4 months | Microglia |
| SA484544 | HSA-000018538 | GPR34-KO | WT | 4 months | Microglia |
| SA484545 | HSA-000018514 | GPR34-KO | WT | 4 months | Microglia |
| SA484546 | HSA-000018526 | GPR34-KO | WT | 4 months | Microglia |
| SA484547 | HSA-000018518 | GPR34-KO | WT | 4 months | Microglia |
| SA484548 | HSA-000018534 | GPR34-KO | WT | 4 months | Microglia |
| SA484549 | HSA-000018546 | GPR34-KO | WT | 4 months | Microglia |
| SA484550 | HSA-000018510 | GPR34-KO | WT | 4 months | Microglia |
| SA484551 | HSA-000018530 | GPR34-KO | WT | 4 months | Microglia |
| SA484552 | HSA-000018542 | GPR34-KO | WT | 4 months | Microglia |
| SA484553 | HSA-000023439 | GPR34-KO | WT | 8 months | Microglia |
| SA484554 | HSA-000023435 | GPR34-KO | WT | 8 months | Microglia |
| SA484555 | HSA-000023411 | GPR34-KO | WT | 8 months | Microglia |
| SA484556 | HSA-000023431 | GPR34-KO | WT | 8 months | Microglia |
| SA484557 | HSA-000023443 | GPR34-KO | WT | 8 months | Microglia |
| SA484558 | HSA-000023427 | GPR34-KO | WT | 8 months | Microglia |
| SA484559 | HSA-000023419 | GPR34-KO | WT | 8 months | Microglia |
| SA484560 | HSA-000023415 | GPR34-KO | WT | 8 months | Microglia |
| SA484561 | HSA-000023447 | GPR34-KO | WT | 8 months | Microglia |
| SA484562 | HSA-000023423 | GPR34-KO | WT | 8 months | Microglia |
| SA484563 | HSA-000031373 | NA | NA | 16 months | Microglia |
| SA484564 | HSA-000031374 | NA | NA | 16 months | Microglia |
| SA484565 | HSA-000030102 | NA | NA | 16 months | Microglia |
| SA484566 | HSA-000021340 | NA | NA | 4 months | Microglia |
| SA484567 | HSA-000021339 | NA | NA | 4 months | Microglia |
| SA484568 | HSA-000021341 | NA | NA | 4 months | Microglia |
| SA484569 | HSA-000023452 | NA | NA | 8 months | Microglia |
| SA484570 | HSA-000023451 | NA | NA | 8 months | Microglia |
| SA484571 | HSA-000023450 | NA | NA | 8 months | Microglia |
| SA484572 | HSA-000030096 | WT | APP-KI | 16 months | Microglia |
| SA484573 | HSA-000030084 | WT | APP-KI | 16 months | Microglia |
| SA484574 | HSA-000030097 | WT | APP-KI | 16 months | Microglia |
| SA484575 | HSA-000030098 | WT | APP-KI | 16 months | Microglia |
| SA484576 | HSA-000030086 | WT | APP-KI | 16 months | Microglia |
| SA484577 | HSA-000030085 | WT | APP-KI | 16 months | Microglia |
| SA484578 | HSA-000036515 | WT | APP-KI | 24 months | Microglia |
| SA484579 | HSA-000035574 | WT | APP-KI | 24 months | Microglia |
| SA484580 | HSA-000036516 | WT | APP-KI | 24 months | Microglia |
| SA484581 | HSA-000036517 | WT | APP-KI | 24 months | Microglia |
| SA484582 | HSA-000035566 | WT | APP-KI | 24 months | Microglia |
| SA484583 | HSA-000035575 | WT | APP-KI | 24 months | Microglia |
| SA484584 | HSA-000035571 | WT | APP-KI | 24 months | Microglia |
| SA484585 | HSA-000035572 | WT | APP-KI | 24 months | Microglia |
| SA484586 | HSA-000035569 | WT | APP-KI | 24 months | Microglia |
| SA484587 | HSA-000035568 | WT | APP-KI | 24 months | Microglia |
| SA484588 | HSA-000035573 | WT | APP-KI | 24 months | Microglia |
| SA484589 | HSA-000035567 | WT | APP-KI | 24 months | Microglia |
| SA484590 | HSA-000035570 | WT | APP-KI | 24 months | Microglia |
| SA484591 | HSA-000018528 | WT | APP-KI | 4 months | Microglia |
| SA484592 | HSA-000018524 | WT | APP-KI | 4 months | Microglia |
| SA484593 | HSA-000018532 | WT | APP-KI | 4 months | Microglia |
| SA484594 | HSA-000018516 | WT | APP-KI | 4 months | Microglia |
| SA484595 | HSA-000018540 | WT | APP-KI | 4 months | Microglia |
| SA484596 | HSA-000018536 | WT | APP-KI | 4 months | Microglia |
| SA484597 | HSA-000018512 | WT | APP-KI | 4 months | Microglia |
| SA484598 | HSA-000018548 | WT | APP-KI | 4 months | Microglia |
Collection:
| Collection ID: | CO004351 |
| Collection Summary: | Microglia were isolated/sorted from mouse brains by fluorescence-activated cell sorting (FACS, Miltenyi Biotec), yielding ~20,000–100,000 cells per animal. |
| Sample Type: | Microglia |
| Storage Conditions: | -80℃ |
| Collection Vials: | Lobind 1.5 mL Eppendorf tubes |
| Storage Vials: | Lobind 1.5 mL Eppendorf tubes |
Treatment:
| Treatment ID: | TR004367 |
| Treatment Summary: | No treatment |
Sample Preparation:
| Sampleprep ID: | SP004364 |
| Sampleprep Summary: | For sorted microglia from mouse brain, 20,000-100,0000 microglia per brain were sorted directly into 400 µl of MS-grade methanol containing stable-isotope internal standards. Samples were vortexed, adjusted to 600 µl with MS-grade H₂O. 600 µl of Methyl tert-butyl ether (MTBE) was added,the samples vortexed and centrifuged at 21,000 g for 10 min at 4 °C. Two phases were observed: a top layer containing non-polar lipids and a bottom layer containing polar metabolites. The lipid phase was collected into glass vials, dried overnight in a Genevac EZ3, and resuspended in 100 µl methanol for lipid LC-MS/MS analysis. |
| Processing Storage Conditions: | On ice |
| Extract Storage: | -20℃ |
Chromatography:
| Chromatography ID: | CH005311 |
| 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: | CH005312 |
| 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 |
Analysis:
| Analysis ID: | AN006995 |
| Analysis Type: | MS |
| Chromatography ID: | CH005311 |
| Num Factors: | 17 |
| Num Metabolites: | 140 |
| Units: | normalized peak area |
| Analysis ID: | AN006996 |
| Analysis Type: | MS |
| Chromatography ID: | CH005312 |
| Num Factors: | 17 |
| Num Metabolites: | 118 |
| Units: | normalized peak area |
