Summary of Study ST002389

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 PR001536. The data can be accessed directly via it's Project DOI: 10.21228/M8512J This work is supported by NIH grant, U2C- DK119886.

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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 IDST002389
Study TitleAlterations in SHH signal transduction introduce a state of hypometabolism in sporadic Parkinson's disease
Study SummaryInduced pluripotent stem cells (iPSC) derived from sporadic Parkinson's disease patients and healthy control subjects were used for disease modeling. iPSC were differentiated towards midbrain dopaminergic neurons. For metabolic analysis, midbrain neuronal precursor cells were cultivated in growth medium supplemented with either 1.25 mM [U-13C]-glutamine or 21.25 mM [U-13C]-glucose. Metabolites were extracted and analyzed using GC-MS. The MetaboliteDetector software was used to analyze chromatograms, calculate mass isotopomer distributions (MIDs) and perform relative comparison of metabolite levels.
Institute
Helmholtz Centre for Environmental Research
DepartmentInstitute of Developmental Genetics
Last NameSchmidt
First NameSebastian
AddressIngolstädter Landstraße 1, 85764 Munich, Germany
Emailsebastian.schmidt@helmholtz-muenchen.de
Phone+4989318743660
Submit Date2022-12-03
Num Groups3
Total Subjects13
Raw Data AvailableYes
Raw Data File Type(s)bin
Analysis Type DetailGC-MS
Release Date2023-10-06
Release Version1
Sebastian Schmidt Sebastian Schmidt
https://dx.doi.org/10.21228/M8512J
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:


Project:

Project ID:PR001536
Project DOI:doi: 10.21228/M8512J
Project Title:Alterations in SHH signal transduction introduce a state of hypometabolism in sporadic Parkinson's disease
Project Type:Isotopic labeling
Project Summary:Sporadic Parkinson’s Disease (sPD) is a progressive neurodegenerative disorder caused by multiple genetic and environmental factors with largely unknown etiology. Prominent pathological culprits include metabolic as well as mitochondrial alterations which have been identified in patients, however, their relevance at different stages of disease progression or their connection remains largely elusive. Here, human iPSCs from late-onset sPD patients were used for disease modeling. Following long-term in vitro cultivation, exclusively neural cells derived from sPD patients developed reduced mitochondrial respiration and glucose consumption reflecting an sPD-specific state of hypometabolism. A multilayered omics analysis based on transcriptomics, proteomics, and metabolomics allowed us to identify the citric acid cycle as being the bottleneck in sPD metabolism. A 13C metabolic flux analysis further unraveled the a-ketoglutarate dehydrogenase complex as being central for a reduced flux through the citric acid cycle. This resulted in a substrate availability problem for the electron transport chain and thus reduced mitochondrial oxygen consumption and ATP production. Notably, these alterations in cellular metabolism were evoked by altered SHH signal transduction due to dysfunctional primary cilia. Upon inhibiting the enhanced SHH signal transduction in sPD, glucose uptake and the activity of the a-ketoglutarate dehydrogenase complex could be restored. Thus, inhibiting overactive SHH signaling may be a potential neuroprotective therapy during the early stages of sPD.
Institute:Helmholtz Centre for Environmental Research
Department:Institute of Developmental Genetics
Last Name:Schmidt
First Name:Sebastian
Address:Ingolstädter Landstraße 1, 85764 Munich, Germany
Email:sebastian.schmidt@helmholtz-muenchen.de
Phone:+4989318743660
Contributors:Karsten Hiller, Alexander Heinz

Subject:

Subject ID:SU002478
Subject Type:Cultured cells
Subject Species:Homo sapiens
Taxonomy ID:9606
Gender:Male and female
Cell Biosource Or Supplier:ForIPS consortium
Cell Strain Details:Midbrain neuronal precursor cells differentiated from patient derived induced pluripotent stem cells
Species Group:Mammals

Factors:

Subject type: Cultured cells; Subject species: Homo sapiens (Factor headings shown in green)

mb_sample_id local_sample_id disease_state 13C_label
SA238064blank_3_Glcblank Glucose
SA238065blank_2_Glcblank Glucose
SA238066blank_1_Glcblank Glucose
SA238067blank_3_Glnblank Glutamine
SA238068blank_1_Glnblank Glutamine
SA238069blank_2_Glnblank Glutamine
SA238070iG3G-R1-039_2_Glcctrl Glucose
SA238071iG3G-R1-039_3_Glcctrl Glucose
SA238072iG3G-R1-039_1_Glcctrl Glucose
SA238073i1JF-R1-018_3_Glcctrl Glucose
SA238074i1JF-R1-018_1_Glcctrl Glucose
SA238075i1E4-R1-003_2_Glcctrl Glucose
SA238076i1E4-R1-003_1_Glcctrl Glucose
SA238077i1JF-R1-018_2_Glcctrl Glucose
SA238078iO3H-R1-005_2_Glcctrl Glucose
SA238079i1E4-R1-003_3_Glcctrl Glucose
SA238080i82A-R1-002_3_Glcctrl Glucose
SA238081iO3H-R1-005_3_Glcctrl Glucose
SA238082iO3H-R1-005_1_Glcctrl Glucose
SA238083i82A-R1-002_2_Glcctrl Glucose
SA238084i82A-R1-002_1_Glcctrl Glucose
SA238085i1E4-R1-003_1_Glnctrl Glutamine
SA238086iG3G-R1-039_3_Glnctrl Glutamine
SA238087i1JF-R1-018_2_Glnctrl Glutamine
SA238088i1E4-R1-003_2_Glnctrl Glutamine
SA238089i1JF-R1-018_3_Glnctrl Glutamine
SA238090iG3G-R1-039_2_Glnctrl Glutamine
SA238091iO3H-R1-005_3_Glnctrl Glutamine
SA238092i82A-R1-002_3_Glnctrl Glutamine
SA238093i1JF-R1-018_1_Glnctrl Glutamine
SA238094i82A-R1-002_2_Glnctrl Glutamine
SA238095i82A-R1-002_1_Glnctrl Glutamine
SA238096iO3H-R1-005_1_Glnctrl Glutamine
SA238097iO3H-R1-005_2_Glnctrl Glutamine
SA238098i1E4-R1-003_3_Glnctrl Glutamine
SA238099iG3G-R1-039_1_Glnctrl Glutamine
SA238100iJ2C-R1-015_3_GlcsPD Glucose
SA238101iJ2C-R1-015_2_GlcsPD Glucose
SA238102iJ2C-R1-015_1_GlcsPD Glucose
SA238103iC99-R1-007_3_GlcsPD Glucose
SA238104iM89-R1-005_1_GlcsPD Glucose
SA238105iM89-R1-005_2_GlcsPD Glucose
SA238106iC99-R1-007_1_GlcsPD Glucose
SA238107i88H-R1-002_3_GlcsPD Glucose
SA238108iM89-R1-005_3_GlcsPD Glucose
SA238109iR66-R1-007_1_GlcsPD Glucose
SA238110iC99-R1-007_2_GlcsPD Glucose
SA238111iPX7-R1-001_2_GlcsPD Glucose
SA238112iR66-R1-007_2_GlcsPD Glucose
SA238113i88H-R1-002_1_GlcsPD Glucose
SA238114i88H-R1-002_2_GlcsPD Glucose
SA238115iPX7-R1-001_1_GlcsPD Glucose
SA238116iPX7-R1-001_3_GlcsPD Glucose
SA238117iR66-R1-007_3_GlcsPD Glucose
SA238118iAY6-R1-003_3_GlcsPD Glucose
SA238119iAY6-R1-003_1_GlcsPD Glucose
SA238120iAY6-R1-003_2_GlcsPD Glucose
SA238121iPX7-R1-001_2_GlnsPD Glutamine
SA238122iPX7-R1-001_1_GlnsPD Glutamine
SA238123iPX7-R1-001_3_GlnsPD Glutamine
SA238124i88H-R1-002_3_GlnsPD Glutamine
SA238125iAY6-R1-003_3_GlnsPD Glutamine
SA238126i88H-R1-002_2_GlnsPD Glutamine
SA238127i88H-R1-002_1_GlnsPD Glutamine
SA238128iC99-R1-007_1_GlnsPD Glutamine
SA238129iM89-R1-005_1_GlnsPD Glutamine
SA238130iM89-R1-005_2_GlnsPD Glutamine
SA238131iJ2C-R1-015_3_GlnsPD Glutamine
SA238132iJ2C-R1-015_2_GlnsPD Glutamine
SA238133iJ2C-R1-015_1_GlnsPD Glutamine
SA238134iM89-R1-005_3_GlnsPD Glutamine
SA238135iC99-R1-007_2_GlnsPD Glutamine
SA238136iR66-R1-007_3_GlnsPD Glutamine
SA238137iAY6-R1-003_1_GlnsPD Glutamine
SA238138iR66-R1-007_2_GlnsPD Glutamine
SA238139iR66-R1-007_1_GlnsPD Glutamine
SA238140iC99-R1-007_3_GlnsPD Glutamine
SA238141iAY6-R1-003_2_GlnsPD Glutamine
Showing results 1 to 78 of 78

Collection:

Collection ID:CO002471
Collection Summary:Neuronal precursor cells differentiated from patient derived induced pluripotent stem cells were seeded on Geltrex coated 6-well plates containing neuronal precursor maintenance medium at a density of 1,000,000 cells/well with six replicates per cell line. hNPCs were cultured at 37 °C, 7 % CO2, 21 % O2 for at least 72 h.
Sample Type:Neurons
Storage Conditions:-80?

Treatment:

Treatment ID:TR002490
Treatment Summary:Growth medium was replaced by a labeling medium containing the respective stable-isotope tracer instead of its unlabeled variant. Cells were cultured with either 1.25 mM [U-13C]-glutamine or 21.25 mM [U-13C]-glucose for 24 h.

Sample Preparation:

Sampleprep ID:SP002484
Sampleprep Summary:Subsequently, cell culture supernatant was stored for profiling the extracellular metabolome. Three replicates per cell line and blanks were washed with 0.9% NaCl and quenched with ice-cold methanol and ice-cold ddH2O (containing 1 µg/ml D6-glutaric acid as internal standard). Cells were scraped and extracts were added into tubes containing ice-cold chloroform. Following vortexing at 1,400 rpm for 20 min at 4°C and centrifugation at 17,000 g for 5 min at 4°C, 300 µl of the polar phase were transferred into GC glass vials with microinsert and dried under vacuum at 4°C. Dried extracts were derivatized using equal amounts of methoxylamine (20 mg/ml in pyridine) and MTBSTFA.

Combined analysis:

Analysis ID AN003893
Analysis type MS
Chromatography type GC
Chromatography system Agilent 7890B gas chromatograph
Column 30 m DB-35 ms and 5 m Duruguard capillary column
MS Type EI
MS instrument type Single quadrupole
MS instrument name Agilent 5977
Ion Mode POSITIVE
Units Mass isotopomer distributions

Chromatography:

Chromatography ID:CH002883
Instrument Name:Agilent 7890B gas chromatograph
Column Name:30 m DB-35 ms and 5 m Duruguard capillary column
Chromatography Type:GC

MS:

MS ID:MS003633
Analysis ID:AN003893
Instrument Name:Agilent 5977
Instrument Type:Single quadrupole
MS Type:EI
MS Comments:One microliter sample was injected into an SSL injector at 270 °C in a split or splitless mode. GC-MS analysis was performed using an Agilent 7890B gas chromatograph equipped with a 30 m DB-35 ms and 5 m Duruguard capillary column. Metabolites were detected in selected ion mode by an Agilent 5977 MSD system. The MetaboliteDetector software was used to analyze chromatograms, calculate mass isotopomer distributions (MIDs) and perform relative comparison of metabolite levels.
Ion Mode:POSITIVE
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