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.

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Study IDST003162
Study TitleLoss of dihydroceramide desaturase drives neurodegeneration by disrupting endoplasmic reticulum and lipid droplet homeostasis in glial cells
Study TypeUntargeted Metabolomics & Lipidomics
Study SummaryDihydroceramide 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
DepartmentGenetics, Medicine, Chemistry
LaboratorySkeath and Patti Laboratories
Last NameCho
First NameKevin
Address1 Brookings Drive, Campus Box 1134, St. Louis, MO, 63130, USA
Emailkevin.cho@wustl.edu
Phone314-935-8813
Submit Date2024-04-09
Raw Data AvailableYes
Raw Data File Type(s)mzML
Analysis Type DetailLC-MS
Release Date2024-04-12
Release Version1
Kevin Cho Kevin Cho
https://dx.doi.org/10.21228/M8G72D
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Factors:

Subject type: Insect; Subject species: Drosophila melanogaster (Factor headings shown in green)

mb_sample_id local_sample_id Genotype Sample source
SA342859CNS_RPLC_POS_ifc_5Knockout CNS
SA342860CNS_RPLC_POS_ifc_4Knockout CNS
SA342861CNS_RPLC_POS_ifc_2Knockout CNS
SA342862CNS_HILIC_NEG_ifc_1Knockout CNS
SA342863CNS_RPLC_POS_ifc_1Knockout CNS
SA342864CNS_HILIC_NEG_ifc_2Knockout CNS
SA342865CNS_HILIC_NEG_ifc_5Knockout CNS
SA342866CNS_HILIC_NEG_ifc_4Knockout CNS
SA342867CNS_HILIC_NEG_ifc_3Knockout CNS
SA342868CNS_RPLC_POS_ifc_3Knockout CNS
SA342869WL_HILIC_NEG_ifc_2Knockout Whole Larvae
SA342870WL_HILIC_NEG_ifc_5Knockout Whole Larvae
SA342871WL_RPLC_POS_ifc_1Knockout Whole Larvae
SA342872WL_HILIC_NEG_ifc_4Knockout Whole Larvae
SA342873WL_HILIC_NEG_ifc_3Knockout Whole Larvae
SA342874WL_HILIC_NEG_ifc_1Knockout Whole Larvae
SA342875WL_RPLC_POS_ifc_5Knockout Whole Larvae
SA342876WL_RPLC_POS_ifc_2Knockout Whole Larvae
SA342877WL_RPLC_POS_ifc_3Knockout Whole Larvae
SA342878WL_RPLC_POS_ifc_4Knockout Whole Larvae
SA342879CNS_HILIC_NEG_WT_2Wild-type CNS
SA342880CNS_RPLC_POS_WT_3Wild-type CNS
SA342881CNS_HILIC_NEG_WT_3Wild-type CNS
SA342882CNS_HILIC_NEG_WT_1Wild-type CNS
SA342883CNS_HILIC_NEG_WT_5Wild-type CNS
SA342884CNS_RPLC_POS_WT_4Wild-type CNS
SA342885CNS_RPLC_POS_WT_5Wild-type CNS
SA342886CNS_RPLC_POS_WT_2Wild-type CNS
SA342887CNS_RPLC_POS_WT_1Wild-type CNS
SA342888CNS_HILIC_NEG_WT_4Wild-type CNS
SA342889WL_HILIC_NEG_WT_4Wild-type Whole Larvae
SA342890WL_RPLC_POS_WT_3Wild-type Whole Larvae
SA342891WL_RPLC_POS_WT_4Wild-type Whole Larvae
SA342892WL_RPLC_POS_WT_5Wild-type Whole Larvae
SA342893WL_HILIC_NEG_WT_1Wild-type Whole Larvae
SA342894WL_HILIC_NEG_WT_2Wild-type Whole Larvae
SA342895WL_RPLC_POS_WT_2Wild-type Whole Larvae
SA342896WL_HILIC_NEG_WT_5Wild-type Whole Larvae
SA342897WL_HILIC_NEG_WT_3Wild-type Whole Larvae
SA342898WL_RPLC_POS_WT_1Wild-type Whole Larvae
Showing results 1 to 40 of 40
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