Summary of Study ST003162
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 PR001967. The data can be accessed directly via it's Project DOI: 10.21228/M8G72D 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 | ST003162 |
| Study Title | Loss of dihydroceramide desaturase drives neurodegeneration by disrupting endoplasmic reticulum and lipid droplet homeostasis in glial cells |
| Study Type | Untargeted Metabolomics & Lipidomics |
| Study Summary | Dihydroceramide desaturases convert dihydroceramides to ceramides, the precursors of all complex sphingolipids. Reduction of DEGS1 dihydroceramide desaturase function causes pediatric neurodegenerative disorder hypomyelinating leukodystrophy-18 (HLD-18). We discovered that infertile crescent (ifc), the Drosophila DEGS1 homolog, is expressed primarily in glial cells to promote CNS development by guarding against neurodegeneration. Loss of ifc causes massive dihydroceramide accumulation and severe morphological defects in cortex glia, including endoplasmic reticulum (ER) expansion, failure of neuronal ensheathment, and lipid droplet depletion. RNAi knockdown of the upstream ceramide synthase schlank in glia of ifc mutants rescues ER expansion, suggesting dihydroceramide accumulation in the ER drives this phenotype. RNAi knockdown of ifc in glia but not neurons drives neuronal cell death, suggesting that ifc function in glia promotes neuronal survival. Our work identifies glia as the primary site of disease progression in HLD-18 and may inform on juvenile forms of ALS, which also feature elevated dihydroceramide levels. |
| Institute | Washington University in St. Louis |
| Department | Genetics, Medicine, Chemistry |
| Laboratory | Skeath and Patti Laboratories |
| Last Name | Cho |
| First Name | Kevin |
| Address | 1 Brookings Drive, Campus Box 1134, St. Louis, MO, 63130, USA |
| kevin.cho@wustl.edu | |
| Phone | 314-935-8813 |
| Submit Date | 2024-04-09 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzML |
| Analysis Type Detail | LC-MS |
| Release Date | 2024-04-12 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Combined analysis:
| Analysis ID | AN005187 | AN005188 | AN005189 | AN005190 |
|---|---|---|---|---|
| Analysis type | MS | MS | MS | MS |
| Chromatography type | HILIC | HILIC | Reversed phase | Reversed phase |
| Chromatography system | Thermo Vanquish Flex UHPLC Systems | Thermo Vanquish Flex UHPLC Systems | Agilent 1290 Infinity II | Agilent 1290 Infinity II |
| Column | HILICON iHILIC-(P) Classic (100 x 2.1mm,5um) | HILICON iHILIC-(P) Classic (100 x 2.1mm,5um) | Waters ACQUITY UPLC HSS T3 (150 x 2.1mm,1.7um) | Waters ACQUITY UPLC HSS T3 (150 x 2.1mm,1.7um) |
| MS Type | ESI | ESI | ESI | ESI |
| MS instrument type | Orbitrap | Orbitrap | QTOF | Orbitrap |
| MS instrument name | Thermo Orbitrap ID-X tribrid | Thermo Orbitrap ID-X tribrid | Agilent 6545 QTOF | Thermo Orbitrap ID-X tribrid |
| Ion Mode | NEGATIVE | NEGATIVE | POSITIVE | POSITIVE |
| Units | peak area | peak area | peak area | peak area |
Chromatography:
| Chromatography ID: | CH003924 |
| Instrument Name: | Thermo Vanquish Flex UHPLC Systems |
| Column Name: | HILICON iHILIC-(P) Classic (100 x 2.1mm,5um) |
| Column Temperature: | 45 |
| Flow Gradient: | 0–1 min: 90% B, 1–12 min: 90-35% B, 12–12.5 min: 35-25% B, 12.5–14.5 min: 25% B |
| Flow Rate: | 250 uL/min |
| Solvent A: | water/acetonitrile (95/5); 20 mM ammonium bicarbonate; 0.1% ammonium hydroxide; 2.5 μM medronic acid |
| Solvent B: | acetonitrile/water (95/5) |
| Chromatography Type: | HILIC |
| Chromatography ID: | CH003925 |
| Instrument Name: | Agilent 1290 Infinity II |
| Column Name: | Waters ACQUITY UPLC HSS T3 (150 x 2.1mm,1.7um) |
| Column Temperature: | 60 |
| Flow Gradient: | 0-2min: 30% B, 2-17 min: 30%-75% B, 17-20 min: 75%-85% B, 20-23 min: 85%-100% B, 23-26 min: 100% B |
| Flow Rate: | 250 uL/min |
| Solvent A: | acetronitrile/water (60/40); 10mM ammonium formate; 2.5 uM medronic acid; 0.1% formic acid |
| Solvent B: | 2-propanol/acetonitrile (90/10); 10mM ammonium formate; 0.1% formic acid |
| Chromatography Type: | Reversed phase |
