{
"METABOLOMICS WORKBENCH":{"STUDY_ID":"ST002739","ANALYSIS_ID":"AN004442","VERSION":"1","CREATED_ON":"08-09-2023"},

"PROJECT":{"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)","DOI":"http://dx.doi.org/10.21228/M8FM85"},

"STUDY":{"STUDY_TITLE":"Metabolic effect of Lamin A/C in oligodendrocyte on brain function","STUDY_TYPE":"LC-MS/MS metabolomics of cell type specific Lmna conditional knockout and wildtype mice brains at 26 weeks","STUDY_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","SUBMIT_DATE":"2023-06-20"},

"SUBJECT":{"SUBJECT_TYPE":"Mammal","SUBJECT_SPECIES":"Mus musculus","TAXONOMY_ID":"10090","AGE_OR_AGE_RANGE":"26 weeks","GENDER":"Female"},
"SUBJECT_SAMPLE_FACTORS":[
{
"Subject ID":"-",
"Sample ID":"KO1_001",
"Factors":{"genotype":"Lmna Knock-Out"},
"Additional sample data":{"RAW_FILE_NAME":"KO1_001_RB4_1_6141.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"KO1_002",
"Factors":{"genotype":"Lmna Knock-Out"},
"Additional sample data":{"RAW_FILE_NAME":"KO1_002_RB4_1_6149.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"KO1_003",
"Factors":{"genotype":"Lmna Knock-Out"},
"Additional sample data":{"RAW_FILE_NAME":"KO1_003_RB4_1_6157.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"KO1_004",
"Factors":{"genotype":"Lmna Knock-Out"},
"Additional sample data":{"RAW_FILE_NAME":"KO1_004_RB4_1_6165.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"KO2_001",
"Factors":{"genotype":"Lmna Knock-Out"},
"Additional sample data":{"RAW_FILE_NAME":"KO2_001_RB5_1_6142.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"KO2_002",
"Factors":{"genotype":"Lmna Knock-Out"},
"Additional sample data":{"RAW_FILE_NAME":"KO2_002_RB5_1_6150.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"KO2_003",
"Factors":{"genotype":"Lmna Knock-Out"},
"Additional sample data":{"RAW_FILE_NAME":"KO2_003_RB5_1_6158.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"KO2_004",
"Factors":{"genotype":"Lmna Knock-Out"},
"Additional sample data":{"RAW_FILE_NAME":"KO2_004_RB5_1_6166.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"KO3_001",
"Factors":{"genotype":"Lmna Knock-Out"},
"Additional sample data":{"RAW_FILE_NAME":"KO3_001_RB6_1_6143.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"KO3_002",
"Factors":{"genotype":"Lmna Knock-Out"},
"Additional sample data":{"RAW_FILE_NAME":"KO3_002_RB6_1_6151.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"KO3_003",
"Factors":{"genotype":"Lmna Knock-Out"},
"Additional sample data":{"RAW_FILE_NAME":"KO3_003_RB6_1_6159.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"KO3_004",
"Factors":{"genotype":"Lmna Knock-Out"},
"Additional sample data":{"RAW_FILE_NAME":"KO3_004_RB6_1_6167.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"WT1_001",
"Factors":{"genotype":"Wild-type"},
"Additional sample data":{"RAW_FILE_NAME":"WT1_001_RB1_1_6137.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"WT1_002",
"Factors":{"genotype":"Wild-type"},
"Additional sample data":{"RAW_FILE_NAME":"WT1_002_RB1_1_6145.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"WT1_003",
"Factors":{"genotype":"Wild-type"},
"Additional sample data":{"RAW_FILE_NAME":"WT1_003_RB1_1_6153.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"WT1_004",
"Factors":{"genotype":"Wild-type"},
"Additional sample data":{"RAW_FILE_NAME":"WT1_004_RB1_1_6161.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"WT2_001",
"Factors":{"genotype":"Wild-type"},
"Additional sample data":{"RAW_FILE_NAME":"WT2_001_RB2_1_6138.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"WT2_002",
"Factors":{"genotype":"Wild-type"},
"Additional sample data":{"RAW_FILE_NAME":"WT2_002_RB2_1_6146.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"WT2_003",
"Factors":{"genotype":"Wild-type"},
"Additional sample data":{"RAW_FILE_NAME":"WT2_003_RB2_1_6154.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"WT2_004",
"Factors":{"genotype":"Wild-type"},
"Additional sample data":{"RAW_FILE_NAME":"WT2_004_RB2_1_6162.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"WT3_001",
"Factors":{"genotype":"Wild-type"},
"Additional sample data":{"RAW_FILE_NAME":"WT3_001_RB3_1_6139.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"WT3_002",
"Factors":{"genotype":"Wild-type"},
"Additional sample data":{"RAW_FILE_NAME":"WT3_002_RB3_1_6147.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"WT3_003",
"Factors":{"genotype":"Wild-type"},
"Additional sample data":{"RAW_FILE_NAME":"WT3_003_RB3_1_6155.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"WT3_004",
"Factors":{"genotype":"Wild-type"},
"Additional sample data":{"RAW_FILE_NAME":"WT3_004_RB3_1_6163.mzML"}
}
],
"COLLECTION":{"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_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"},

"SAMPLEPREP":{"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"},

"CHROMATOGRAPHY":{"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"},

"ANALYSIS":{"ANALYSIS_TYPE":"MS"},

"MS":{"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","MS_RESULTS_FILE":"ST002739_AN004442_Results.txt UNITS:peak area Has m/z:Yes Has RT:Yes RT units:Minutes"}

}