Summary of Study ST003629

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 PR002242. The data can be accessed directly via it's Project DOI: 10.21228/M8TK06 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 IDST003629
Study TitleImpact of human PSMC5 gene mutations on neuronal development: Lipid profiling of PSMC5 mutant T cells
Study Typeexplorative
Study SummaryA massive enrichment of apolipoproteins prompted us to investigate lipid compositions of T cell samples of patients versus healthy controls. Surprisingly, we observed a massively altered distribution of lipids in samples of patients with PSMC5 variants. Thus, phospholipids of membranes such as phosphatidylserine (PS), phosphatidylethanolamine (PE), phosphatidylcholine (PC), as well as di- (DG) or tri-acylglycerols (TG), were significantly decreased in patients, whereas cholesterolesters were increased by 50%.
Institute
Leibniz Institute for Plasma Science and Technology
DepartmentZIK
LaboratoryPlasma Liquid Effects
Last NameKristian
First NameWende
AddressFelix-Hausdorff-Str. 2, D-17489 Greifswald
Emailkristian.wende@inp-greifswald.de
Phone+49 3834 554 3923
Submit Date2024-12-09
Total Subjects11
Raw Data AvailableYes
Raw Data File Type(s)mzML, raw(Thermo)
Analysis Type DetailLC-MS
Release Date2025-09-15
Release Version1
Wende Kristian Wende Kristian
https://dx.doi.org/10.21228/M8TK06
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

Project:

Project ID:PR002242
Project DOI:doi: 10.21228/M8TK06
Project Title:Impact of human PSMC5 gene mutations on neuronal development
Project Summary:Our study identified 23 unique variants in PSMC5, which encodes the AAA-ATPase proteasome subunit PSMC5/Rpt6, causing syndromic Neurodevelopmental Disorder (NDD) in 38 unrelated individuals. PSMC5 loss-of-function resulted in abnormal protein aggregation, profoundly affecting innate immune signaling, mitophagy rate, and lipid metabolism in affected individuals’ samples. These findings deepen our understanding of the molecular mechanisms underlying neurodevelopmental proteasomopathies and link these disorders with neurodegenerative disease research.
Institute:Nantes Université
Department:Service de Génétique Médicale
Last Name:Sebastien
First Name:Kury
Address:F-44000 Nantes
Email:sebastien.kury@chu-nantes.fr
Phone:02 28 08 01 10
Funding Source:Agence Nationale de la Recherche ANR-21-CE17-0005
Publications:Unveiling the crucial neuronal role of the proteasomal ATPase subunit gene PSMC5 in neurodevelopmental proteasomopathies
Contributors:Sébastien Küry et al.

Subject:

Subject ID:SU003759
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 Variant/Subject alteration in PSMC5 protein comment
SA393479PSMC5_AM_R201W_neg2PSMC5 AM (Pittsburgh) R201W Patient
SA393480PSMC5_AM_R201W_pos1PSMC5 AM (Pittsburgh) R201W Patient
SA393481PSMC5_AM_R201W_pos2PSMC5 AM (Pittsburgh) R201W Patient
SA393482PSMC5_AM_R201W_neg1PSMC5 AM (Pittsburgh) R201W Patient
SA393483PSMC5_AM_BC_neg1PSMC5 BC (Pittsburgh) None Control/mother of AM
SA393484PSMC5_AM_BC_pos1PSMC5 BC (Pittsburgh) None Control/mother of AM
SA393485PSMC5_AM_BC_pos2PSMC5 BC (Pittsburgh) None Control/mother of AM
SA393486PSMC5_AM_BC_neg2PSMC5 BC (Pittsburgh) None Control/mother of AM
SA393487PSMC5_BLG_R325W_neg1PSMC5 BLG (Montpellier) R325W Patient
SA393488PSMC5_BLG_R325W_neg2PSMC5 BLG (Montpellier) R325W Patient
SA393489PSMC5_BLG_R325W_pos1PSMC5 BLG (Montpellier) R325W Patient
SA393490PSMC5_BLG_R325W_pos2PSMC5 BLG (Montpellier) R325W Patient
SA393491PSMC5_BN_E205V_pos2PSMC5 BN (Angers) E205V Patient
SA393492PSMC5_BN_E205V_pos1PSMC5 BN (Angers) E205V Patient
SA393493PSMC5_BN_E205V_neg2PSMC5 BN (Angers) E205V Patient
SA393494PSMC5_BN_E205V_neg1PSMC5 BN (Angers) E205V Patient
SA393495PSMC5_Bro_neg1PSMC5 Bro (Prague) None Control/Brother of DelExon4
SA393496PSMC5_Bro_neg2PSMC5 Bro (Prague) None Control/Brother of DelExon5
SA393497PSMC5_Bro_pos1PSMC5 Bro (Prague) None Control/Brother of DelExon6
SA393498PSMC5_Bro_pos2PSMC5 Bro (Prague) None Control/Brother of DelExon7
SA393499PSMC5_DeltaExon4_neg2PSMC5 DelExon4 (Prague) Delta Exon 4 Patient
SA393500PSMC5_DeltaExon4_neg1PSMC5 DelExon4 (Prague) Delta Exon 4 Patient
SA393501PSMC5_DeltaExon4_pos1PSMC5 DelExon4 (Prague) Delta Exon 4 Patient
SA393502PSMC5_DeltaExon4_pos2PSMC5 DelExon4 (Prague) Delta Exon 4 Patient
SA393503PSMC5_FN_neg1PSMC5 FN (Angers) None Control/father of BN
SA393504PSMC5_FN_neg2PSMC5 FN (Angers) None Control/father of BN
SA393505PSMC5_FN_pos1PSMC5 FN (Angers) None Control/father of BN
SA393506PSMC5_FN_pos2PSMC5 FN (Angers) None Control/father of BN
SA393507PSMC5_PSMD11R90_neg1PSMC5 JFL (Nantes) PSMD11 R90* Control/father of LL
SA393508PSMC5_PSMD11R90_neg2PSMC5 JFL (Nantes) PSMD11 R90* Control/father of LL
SA393509PSMC5_PSMD11R90_pos1PSMC5 JFL (Nantes) PSMD11 R90* Control/father of LL
SA393510PSMC5_PSMD11R90_pos2PSMC5 JFL (Nantes) PSMD11 R90* Control/father of LL
SA393511PSMC5_JLG_pos2PSMC5 JLG (Montpellier) None Control/father of BLG
SA393512PSMC5_JLG_neg2PSMC5 JLG (Montpellier) None Control/father of BLG
SA393513PSMC5_JLG_neg1PSMC5 JLG (Montpellier) None Control/father of BLG
SA393514PSMC5_JLG_pos1PSMC5 JLG (Montpellier) None Control/father of BLG
SA393515PSMC5_JS_P302R_neg1PSMC5 JS (New-York) P320R Patient
SA393516PSMC5_JS_P302R_neg2PSMC5 JS (New-York) P320R Patient
SA393517PSMC5_JS_P302R_pos2PSMC5 JS (New-York) P320R Patient
SA393518PSMC5_JS_P302R_pos1PSMC5 JS (New-York) P320R Patient
SA393519PSMC5_PSMD11R90_Q221R_pos2PSMC5 LL (Nantes) PSMD11R90*/Q221R Patient
SA393520PSMC5_PSMD11R90_Q221R_neg2PSMC5 LL (Nantes) PSMD11R90*/Q221R Patient
SA393521PSMC5_PSMD11R90_Q221R_neg1PSMC5 LL (Nantes) PSMD11R90*/Q221R Patient
SA393522PSMC5_PSMD11R90_Q221R_pos1PSMC5 LL (Nantes) PSMD11R90*/Q221R Patient
Showing results 1 to 44 of 44

Collection:

Collection ID:CO003752
Collection Summary:Whole-blood samples collected from healthy individuals as well as diseased subjects S1 (PSMC_DeltaExon4), S7 (PSMC5_AM_R201W), S14 (PSMC5_PSMD11R90_Q221R), S15 (PSMC5_BN_E205V), and S37 (PSMC5_BLG_R325W) and their respective parents and/or siblings when possible: C1 (sibling to S1), C2 (sibling to S7), C3 (sibling to S14), C4 (sibling to S15), and C5 (sibling to S37) were processed using spin medium gradient centrifugations (pluriSelect) to separate and isolate peripheral blood mononuclear cells (PBMC) for cryopreservation using a standard freezing medium consisting of 90% FBS and 10 % DMSO. At a later point in time, PBMC were plated on 96-well plates together with irradiated allogeneic PBMC in the presence of IL-2 and PHA-L for T cell expansion as in 11. Human T cells were maintained in RPMI1640 supplemented with 10 % human AB serum and 1% penicillin/streptomycin and analyzed at a resting state after 3-4 weeks of expansion.
Sample Type:T-cells

Treatment:

Treatment ID:TR003768
Treatment Summary:No treatment

Sample Preparation:

Sampleprep ID:SP003766
Sampleprep Summary:In brief, 225 μL of cold MeOH w/ 0.01 % BHT was added to an PBMC cell pellet, vortexed and mixed by pipetting up and down, and pulse sonicated using a tip sonicator for 30s on ice. After adding 3 μL of the EquiSPLASH (Avanti Polar Lipids, Alabaster/AL, USA) and 750 μL of cold MTBE the mixture was incubated for 1 h at 4 °C in a thermomixer at 650 rpm. After adding 188 μL of ultrapure water the sample was centrifuged at 10,000 g for 10 min. The upper (organic) layer (700 μL) was transferred to a vial and stored at 4 °C. The lower phase was extracted again with 400 µL MTBE and 10 µL acetic acid for 30 min at 4 °C (thermomixer), and 400 µL of the upper organic layer was transferred to first extract. After drying with sodium sulphate, the solvent was removed by nitrogen stream and stored at -80 °C until analysis.

Chromatography:

Chromatography ID:CH004530
Chromatography Summary:After rehydration with chloroform/methanol/isopropanol (1:2:4; buffered with ammonium acetate pH 8), samples were analyzed in duplicate by a Vanquish UHPLC system equipped with an AccuCore C30 column (2.1x100 mm, 2.6 µm, Thermo Fisher Scientific) connected via nano-electrospray to an QExactive Plus high-resolution mass spectrometer in positive and negative mode (four injections per sample). Separation was achieved at 50 °C using a linear gradient built from: 60:40 water: acetonitrile (v/v, 10 mM ammonium formate/0.1 % formic acid, buffer A) and 90:10 Isopropanol: Acetonitrile (v/v, 10 mM ammonium formate/0.1 % formic acid, buffer B). The composition changed from 20 % B to 99 % B within 29 min.
Instrument Name:Thermo Vanquish
Column Name:Thermo Accucore C30 (150 x 2.1mm,2.6um)
Column Temperature:50
Flow Gradient:Linear gradient: 20% B to 99% B in 29min
Flow Rate:300uL/min
Solvent A:60% water/40% acetonitrile; 10 mM ammonium formate; 0.1 % formic acid
Solvent B:90% isopropanol/10% acetonitrile; 10 mM ammonium formate;0.1 % formic acid
Chromatography Type:Reversed phase

Analysis:

Analysis ID:AN005961
Analysis Type:MS
Chromatography ID:CH004530
Num Factors:14
Num Metabolites:510
Units:z-score normalized area
  
Analysis ID:AN005962
Analysis Type:MS
Chromatography ID:CH004530
Num Factors:14
Num Metabolites:2212
Units:z-score normalized
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