{
"METABOLOMICS WORKBENCH":{"STUDY_ID":"ST002979","ANALYSIS_ID":"AN004895","VERSION":"1","CREATED_ON":"11-21-2023"},

"PROJECT":{"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","DOI":"http://dx.doi.org/10.21228/M8XT6T"},

"STUDY":{"STUDY_TITLE":"Untargeted lipidomics profiling of TSC microglia","STUDY_SUMMARY":"In 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_NAME":"Xie","FIRST_NAME":"Boer","ADDRESS":"262 Danny Thomas Place, Memphis, TN, 38105, USA","EMAIL":"xbr429@gmail.com","PHONE":"(901) 595-7499","SUBMIT_DATE":"2023-11-09"},

"SUBJECT":{"SUBJECT_TYPE":"Cultured cells","SUBJECT_SPECIES":"Homo sapiens","TAXONOMY_ID":"9606"},
"SUBJECT_SAMPLE_FACTORS":[
{
"Subject ID":"-",
"Sample ID":"TSC10-1",
"Factors":{"Genotype":"TSC mutation"},
"Additional sample data":{"RAW_FILE_NAME":"13.raw"}
},
{
"Subject ID":"-",
"Sample ID":"TSC10-2",
"Factors":{"Genotype":"TSC mutation"},
"Additional sample data":{"RAW_FILE_NAME":"14.raw"}
},
{
"Subject ID":"-",
"Sample ID":"TSC10-3",
"Factors":{"Genotype":"TSC mutation"},
"Additional sample data":{"RAW_FILE_NAME":"15.raw"}
},
{
"Subject ID":"-",
"Sample ID":"TSC10-Homo-1",
"Factors":{"Genotype":"TSC mutation"},
"Additional sample data":{"RAW_FILE_NAME":"16.raw"}
},
{
"Subject ID":"-",
"Sample ID":"TSC10-Homo-2",
"Factors":{"Genotype":"TSC mutation"},
"Additional sample data":{"RAW_FILE_NAME":"17.raw"}
},
{
"Subject ID":"-",
"Sample ID":"TSC10-Homo-3",
"Factors":{"Genotype":"TSC mutation"},
"Additional sample data":{"RAW_FILE_NAME":"18.raw"}
},
{
"Subject ID":"-",
"Sample ID":"TSC7-1",
"Factors":{"Genotype":"TSC mutation"},
"Additional sample data":{"RAW_FILE_NAME":"10.raw"}
},
{
"Subject ID":"-",
"Sample ID":"TSC7-2",
"Factors":{"Genotype":"TSC mutation"},
"Additional sample data":{"RAW_FILE_NAME":"11.raw"}
},
{
"Subject ID":"-",
"Sample ID":"TSC7-3",
"Factors":{"Genotype":"TSC mutation"},
"Additional sample data":{"RAW_FILE_NAME":"12.raw"}
},
{
"Subject ID":"-",
"Sample ID":"TSC7-4",
"Factors":{"Genotype":"TSC mutation"},
"Additional sample data":{"RAW_FILE_NAME":"26.raw"}
},
{
"Subject ID":"-",
"Sample ID":"12C1-1",
"Factors":{"Genotype":"wildtype"},
"Additional sample data":{"RAW_FILE_NAME":"19.raw"}
},
{
"Subject ID":"-",
"Sample ID":"12C1-2",
"Factors":{"Genotype":"wildtype"},
"Additional sample data":{"RAW_FILE_NAME":"20.raw"}
},
{
"Subject ID":"-",
"Sample ID":"12C1-3",
"Factors":{"Genotype":"wildtype"},
"Additional sample data":{"RAW_FILE_NAME":"21.raw"}
},
{
"Subject ID":"-",
"Sample ID":"12C1-4",
"Factors":{"Genotype":"wildtype"},
"Additional sample data":{"RAW_FILE_NAME":"22.raw"}
},
{
"Subject ID":"-",
"Sample ID":"426-1",
"Factors":{"Genotype":"wildtype"},
"Additional sample data":{"RAW_FILE_NAME":"04.raw"}
},
{
"Subject ID":"-",
"Sample ID":"426-2",
"Factors":{"Genotype":"wildtype"},
"Additional sample data":{"RAW_FILE_NAME":"05.raw"}
},
{
"Subject ID":"-",
"Sample ID":"426-3",
"Factors":{"Genotype":"wildtype"},
"Additional sample data":{"RAW_FILE_NAME":"06.raw"}
},
{
"Subject ID":"-",
"Sample ID":"426-4",
"Factors":{"Genotype":"wildtype"},
"Additional sample data":{"RAW_FILE_NAME":"24.raw"}
},
{
"Subject ID":"-",
"Sample ID":"C1-2-1",
"Factors":{"Genotype":"wildtype"},
"Additional sample data":{"RAW_FILE_NAME":"01.raw"}
},
{
"Subject ID":"-",
"Sample ID":"C1-2-2",
"Factors":{"Genotype":"wildtype"},
"Additional sample data":{"RAW_FILE_NAME":"02.raw"}
},
{
"Subject ID":"-",
"Sample ID":"C1-2-3",
"Factors":{"Genotype":"wildtype"},
"Additional sample data":{"RAW_FILE_NAME":"03.raw"}
},
{
"Subject ID":"-",
"Sample ID":"C1-2-4",
"Factors":{"Genotype":"wildtype"},
"Additional sample data":{"RAW_FILE_NAME":"23.raw"}
},
{
"Subject ID":"-",
"Sample ID":"PGP1-1",
"Factors":{"Genotype":"wildtype"},
"Additional sample data":{"RAW_FILE_NAME":"07.raw"}
},
{
"Subject ID":"-",
"Sample ID":"PGP1-2",
"Factors":{"Genotype":"wildtype"},
"Additional sample data":{"RAW_FILE_NAME":"08.raw"}
},
{
"Subject ID":"-",
"Sample ID":"PGP1-3",
"Factors":{"Genotype":"wildtype"},
"Additional sample data":{"RAW_FILE_NAME":"09.raw"}
},
{
"Subject ID":"-",
"Sample ID":"PGP1-4",
"Factors":{"Genotype":"wildtype"},
"Additional sample data":{"RAW_FILE_NAME":"25.raw"}
}
],
"COLLECTION":{"COLLECTION_SUMMARY":"Cell line and sample collection were done at Emory University","SAMPLE_TYPE":"Neurons"},

"TREATMENT":{"TREATMENT_SUMMARY":"No treatment applied."},

"SAMPLEPREP":{"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."},

"CHROMATOGRAPHY":{"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"},

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

"MS":{"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_RESULTS_FILE":"ST002979_AN004895_Results.txt UNITS:Intensity Has m/z:Yes Has RT:Yes RT units:Minutes"}

}