Summary of Study ST002739

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 PR001704. The data can be accessed directly via it's Project DOI: 10.21228/M8FM85 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 IDST002739
Study TitleMetabolic effect of Lamin A/C in oligodendrocyte on brain function
Study TypeLC-MS/MS metabolomics of cell type specific Lmna conditional knockout and wildtype mice brains at 26 weeks
Study SummaryOligodendrocytes are specialized cells which insulate and support axons with their myelin membrane, allowing proper brain function. Here, we identify Lamin A/C (LMNA/C) as essential for transcriptional and functional stability of myelinating oligodendrocytes. We show that LMNA/C levels increase with differentiation of progenitors and that loss of Lmna in differentiated oligodendrocytes profoundly alters their chromatin accessibility and transcriptional signature. Lmna deletion in myelinating glia is compatible with normal developmental myelination. However, altered chromatin accessibility is detected in fully differentiated oligodendrocytes together with increased expression of progenitor genes and decreased levels of lipid-related transcription factors and inner mitochondrial membrane transcripts. As mice age, they start to develop myelin-thinning and progressively worsening motor phenotype. To address the metabolic effect of LMNA/C in oligodendrocyte on brain function, we carried out LC-MS/MS metabolomic study of myelinating glia cell specific Lmna conditional knockout and wildtype mice brains at 26 weeks. Each LC-MS/MS experiment was performed with 3 biological replicates and 4 technical replicates per genotype. Overall, our data identify LMNA/C as essential for maintaining the transcriptional and functional stability of myelinating oligodendrocytes.
Institute
Advanced Science Research Center - CUNY
DepartmentNeuroscience
LaboratoryCasaccia lab, He lab, MALDI and MS core.
Last NameHe
First NameYe
Address85 St. Nicholas Terrace, New York, New York, 10031, USA
Emailyhe1@gc.cuny.edu
Phone2124133182
Submit Date2023-06-20
Raw Data AvailableYes
Raw Data File Type(s)mzML
Analysis Type DetailLC-MS
Release Date2023-06-22
Release Version1
Ye He Ye He
https://dx.doi.org/10.21228/M8FM85
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

Project:

Project ID:PR001704
Project DOI:doi: 10.21228/M8FM85
Project Title:Metabolic effect of Lamin A/C in oligodendrocyte on brain function
Project Type:LC-MS/MS metabolomics of cell type specific Lmna conditional knockout and wildtype mice brains at 26 weeks
Project Summary:Oligodendrocytes are specialized cells which insulate and support axons with their myelin membrane, allowing proper brain function. Here, we identify Lamin A/C (LMNA/C) as essential for transcriptional and functional stability of myelinating oligodendrocytes. We show that LMNA/C levels increase with differentiation of progenitors and that loss of Lmna in differentiated oligodendrocytes profoundly alters their chromatin accessibility and transcriptional signature. Lmna deletion in myelinating glia is compatible with normal developmental myelination. However, altered chromatin accessibility is detected in fully differentiated oligodendrocytes together with increased expression of progenitor genes and decreased levels of lipid-related transcription factors and inner mitochondrial membrane transcripts. As mice age, they start to develop myelin-thinning and progressively worsening motor phenotype. To address the metabolic effect of LMNA/C in oligodendrocyte on brain function, we carried out LC-MS/MS metabolomic study of myelinating glia cell specific Lmna conditional knockout and wildtype mice brains at 26 weeks. Each LC-MS/MS experiment was performed with 3 biological replicates and 4 technical replicates per genotype. Overall, our data identify LMNA/C as essential for maintaining the transcriptional and functional stability of myelinating oligodendrocytes.
Institute:Advanced Science Research Center - CUNY
Department:Neuroscience
Laboratory:Casaccia lab, He lab, MALDI and MS core.
Last Name:He
First Name:Ye
Address:85 St. Nicholas Terrace, New York, New York, 10031, USA
Email:yhe1@gc.cuny.edu
Phone:2124133182
Publications:Pruvost M, Patzig J, Yattah C, Selcen I, Hernandez M, Park HJ, Moyon S, Liu S, Morioka MS, Shopland L, Al-Dalahmah O, Bendl J, Fullard JF, Roussos P, Goldman J, He Y, Dupree JL, Casaccia P. The stability of the myelinating oligodendrocyte transcriptome is regulated by the nuclear lamina. Cell Rep. 2023 Jul 27;42(8):112848. doi: 10.1016/j.celrep.2023.112848. Epub ahead of print. PMID: 37515770. (https://www.cell.com/cell-reports/fulltext/S2211-1247(23)00859-8)

Subject:

Subject ID:SU002846
Subject Type:Mammal
Subject Species:Mus musculus
Taxonomy ID:10090
Age Or Age Range:26 weeks
Gender:Female

Factors:

Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)

mb_sample_id local_sample_id genotype
SA288788KO3_002Lmna Knock-Out
SA288789KO3_003Lmna Knock-Out
SA288790KO1_001Lmna Knock-Out
SA288791KO2_004Lmna Knock-Out
SA288792KO3_004Lmna Knock-Out
SA288793KO3_001Lmna Knock-Out
SA288794KO2_003Lmna Knock-Out
SA288795KO1_002Lmna Knock-Out
SA288796KO1_004Lmna Knock-Out
SA288797KO1_003Lmna Knock-Out
SA288798KO2_001Lmna Knock-Out
SA288799KO2_002Lmna Knock-Out
SA288800WT3_002Wild-type
SA288801WT3_001Wild-type
SA288802WT3_004Wild-type
SA288803WT2_004Wild-type
SA288804WT3_003Wild-type
SA288805WT1_001Wild-type
SA288806WT1_003Wild-type
SA288807WT1_002Wild-type
SA288808WT1_004Wild-type
SA288809WT2_001Wild-type
SA288810WT2_002Wild-type
SA288811WT2_003Wild-type
Showing results 1 to 24 of 24

Collection:

Collection ID:CO002839
Collection Summary:Murine brains were harvested at 26 weeks and were snap-frozen for 5 min on an aluminum boat floating on liquid nitrogen.
Sample Type:Brain

Treatment:

Treatment ID:TR002855
Treatment Summary:The experimental group was composed of three 26-week-old female mice with conditional ablation of Lmna in the oligodendrocytes (CnpCre/+;Lmnafl/fl). The control group consisted of three wildtype 26-week-old female mice

Sample Preparation:

Sampleprep ID:SP002852
Sampleprep Summary:A coronal slice of brain (approximate 15 mg) at (-0.88 mm to -1.335mm from Bregma) plane was sectioned and homogenized in cold Methanol/Water (80/20, v/v) to a final concentration of 30mg/ml. Following 20 min of gentle sonication in Bioruptor (30 s on, 30 s off, 20 cycles) at 4 °C, samples were centrifuged for 10 min at 10,000xg at 4 °C and were processed for LC-MS/MS

Combined analysis:

Analysis ID AN004442
Analysis type MS
Chromatography type HILIC
Chromatography system Thermo Dionex Ultimate 3000
Column SeQuant ZIC-HILIC (100 x 2.1mm,3.5um)
MS Type ESI
MS instrument type QTOF
MS instrument name Bruker maXis-II
Ion Mode POSITIVE
Units peak area

Chromatography:

Chromatography ID:CH003337
Instrument Name:Thermo Dionex Ultimate 3000
Column Name:SeQuant ZIC-HILIC (100 x 2.1mm,3.5um)
Column Temperature:30
Flow Gradient:0.15mL/min; 0-5.0 min; 2.0% B, 5.0-28.0 min; 2.0-60.0% B, 28.0-38.0 min; 60.0% B, 38.0-39.0 min; 60.0-2.0% B, 39.0-48.0 min, 2.0% B.
Flow Rate:0.15mL/min
Solvent A:97% acetonitrile/3% water/7mM ammonium acetate
Solvent B:97% water/3% acetonitrile/7mM ammonium acetate
Chromatography Type:HILIC

MS:

MS ID:MS004189
Analysis ID:AN004442
Instrument Name:Bruker maXis-II
Instrument Type:QTOF
MS Type:ESI
MS Comments:MS spectra were obtained using a Bruker maXis-II-ETD UHR-ESI-QTOF, witb Ultra High Resolution QTOF (UHR) technology in addition to Electron-Transfer Dissociation (ETD). Compound identification and descriptive statistical analysis of the LC-MS/MS data were performed through Metaboscape and XCMSPlus software. Bruker MetaboBase Personal 3.0, MoNA, MSDIAL, METLIN, and HMDB metabolomic libraries were used in compound identification. Ultimately, both accurate mass-measurements (with less than 5 pmm accuracy) and fragmentation spectra (or simply MS/MS spectra) were used for confident identification of metabolites and lipids.
Ion Mode:POSITIVE
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