Summary of Study ST002979

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 PR001855. The data can be accessed directly via it's Project DOI: 10.21228/M8XT6T 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 IDST002979
Study TitleUntargeted lipidomics profiling of TSC microglia
Study SummaryIn this study, human microglia from induced pluripotent stem cells (iPSCs) derived from a TSC patient cohort were generated . With a comprehensively molecular and cellular characterization on TSC microglia, including transcriptomics, proteomics/phosphopreteomics, and lipidomics, patient-carrying TSC2 mutations lead to aberrant lipid metabolism were found, in particular, upregulated glycerophosphocholines and fatty acyls in TSC microglia, resulting in increased phagocytosis and inflammation. Strikingly, the dysregulated lipid metabolism in TSC microglia is driven by hyper-activation of mTOR-LPL pathway. Furthermore, cellular and electrophysiological assessments of neuron/microglia co-cultures revealed that TSC microglia directly affect neuronal development and excitability as well as neuronal network activity, which could be largely ameliorated by mTOR/LPL inhibition
Institute
St Jude Children's Research Hospital
Last NameXie
First NameBoer
Address262 Danny Thomas Place, Memphis, TN, 38105, USA
Emailxbr429@gmail.com
Phone(901) 595-7499
Submit Date2023-11-09
Raw Data AvailableYes
Raw Data File Type(s)raw(Thermo)
Analysis Type DetailLC-MS
Release Date2023-11-17
Release Version1
Boer Xie Boer Xie
https://dx.doi.org/10.21228/M8XT6T
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR001855
Project DOI:doi: 10.21228/M8XT6T
Project Title:Integrated multi-omics reveals mTOR-LPL-driven dysregulated lipid metabolism induces neuronal hyperexcitability in human microglia of tuberous sclerosis complex
Project Summary:Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder caused by mutations in either TSC1 or TSC2. There's evidence suggests a connection between microglia activation and epilepsy as well as cognitive impairment in TSC patients. However, how the causal variants of TSC1/2 genes identified in TSC patients affect human microglia and how they contribute to the neurological manifestations. This project is focus on this problem using human microglia generated from induced pluripotent stem cells (iPSCs) derived from a TSC patient.
Institute:St Jude Children's Research Hospital
Last Name:Xie
First Name:Boer
Address:262 Danny Thomas Place, Memphis, TN, 38105, USA
Email:xbr429@gmail.com
Phone:(901) 595-7499

Subject:

Subject ID:SU003092
Subject Type:Cultured cells
Subject Species:Homo sapiens
Taxonomy ID:9606
Species Group:Mammals

Factors:

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

mb_sample_id local_sample_id Genotype
SA323369TSC10-3TSC mutation
SA323370TSC10-1TSC mutation
SA323371TSC7-3TSC mutation
SA323372TSC10-Homo-1TSC mutation
SA323373TSC10-Homo-2TSC mutation
SA323374TSC7-4TSC mutation
SA323375TSC10-Homo-3TSC mutation
SA323376TSC7-2TSC mutation
SA323377TSC10-2TSC mutation
SA323378TSC7-1TSC mutation
SA32337912C1-4wildtype
SA32338012C1-3wildtype
SA323381C1-2-4wildtype
SA323382426-4wildtype
SA323383C1-2-2wildtype
SA323384C1-2-3wildtype
SA323385PGP1-4wildtype
SA32338612C1-2wildtype
SA32338712C1-1wildtype
SA323388PGP1-2wildtype
SA323389PGP1-3wildtype
SA323390C1-2-1wildtype
SA323391PGP1-1wildtype
SA323392426-2wildtype
SA323393426-3wildtype
SA323394426-1wildtype
Showing results 1 to 26 of 26

Collection:

Collection ID:CO003085
Collection Summary:Cell line and sample collection were done at Emory University
Sample Type:Neurons

Treatment:

Treatment ID:TR003101
Treatment Summary:No treatment applied.

Sample Preparation:

Sampleprep ID:SP003098
Sampleprep Summary:Lipids were extracted from cell by cold isopropanol (10:1 v/v, solvent to sample). Extracted lipids were dried under nitrogen gas, resuspended in 65% acetonitrile, 30% isopropanol and 5% water.

Combined analysis:

Analysis ID AN004895 AN004896
Analysis type MS MS
Chromatography type Reversed phase Reversed phase
Chromatography system Waters NanoAcquity Waters NanoAcquity
Column Supelco Ascentis Express C18 (15 cm X 300 µm, 2.7µm) Supelco Ascentis Express C18 (15 cm X 300 µm, 2.7µm)
MS Type ESI ESI
MS instrument type Orbitrap Orbitrap
MS instrument name Thermo Q Exactive HF hybrid Orbitrap Thermo Q Exactive HF hybrid Orbitrap
Ion Mode POSITIVE NEGATIVE
Units Intensity Intensity

Chromatography:

Chromatography ID:CH003694
Chromatography Comments:https://www.sigmaaldrich.com/US/en/product/supelco/54271u
Instrument Name:Waters NanoAcquity
Column Name:Supelco Ascentis Express C18 (15 cm X 300 µm, 2.7µm)
Column Temperature:RT
Flow Gradient:10-75%B in 34min
Flow Rate:-
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

MS:

MS ID:MS004639
Analysis ID:AN004895
Instrument Name:Thermo Q Exactive HF hybrid Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:MS1:120k resolution, 100-1200 m/z, 3e6 AGC, 50 ms maximal ion time MS2:top 20, 30k resolution, 2e5 AGC, 45 ms maximal ion time, stepped HCD NCE at 30, 75, 150 In-house JUMPm software and Shiny were used for data processing, feature assignment and statistic analysis
Ion Mode:POSITIVE
  
MS ID:MS004640
Analysis ID:AN004896
Instrument Name:Thermo Q Exactive HF hybrid Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:MS1:120k resolution, 100-1200 m/z, 3e6 AGC, 50 ms maximal ion time MS2:top 20, 30k resolution, 2e5 AGC, 45 ms maximal ion time, stepped HCD NCE at 30, 75, 150 In-house JUMPm software and Shiny were used for data processing, feature assignment and statistic analysis
Ion Mode:NEGATIVE
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