{
"METABOLOMICS WORKBENCH":{"STUDY_ID":"ST003244","ANALYSIS_ID":"AN005314","PROJECT_ID":"PR002014","VERSION":"1","CREATED_ON":"June 7, 2024, 11:12 am"},

"PROJECT":{"PROJECT_TITLE":"Suppression of prostaglandin I2–type I interferon axis induces extramedullary hematopoiesis to promote cardiac repair after myocardial infarction","PROJECT_SUMMARY":"Background: Immune cells are closely associated with all processes of cardiac repair following myocardial infarction (MI), including the initiation, development, and resolution of inflammation. Spleen extramedullary hematopoiesis (EMH) serves as a critical source of emergency mature blood cells that are generated through the self-renewal and differentiation of hematopoietic stem/progenitor cells (HSPCs). However, how EMH responds to MI and the role of EMH in cardiac repair post-MI remains unclear. Methods: To assess the role of spleen EMH in MI, a Tcf21CreERScfflox/flox MI mouse model with inhibited EMH was constructed. GFP+ HSCs sorted from eGFP mouse spleen by flow cytometry and injected into Tcf21CreERScfflox/flox mice to test the sources of local inflammatory cells during MI. Using highly specific liquid chromatography-tandem mass spectrometry and single-cell RNA sequencing, we analyzed the lipidomic profile of arachidonic acid metabolites and the transcriptomes of HSPCs in the spleen after MI. Results: We found that MI enhanced EMH, as reflected by the increase in spleen weight and volume and the number of HSPCs in the spleen. The lack of EMH in Scf-deficient mice exacerbated tissue injury post-MI. Analyzing the transcriptome of spleen HSPCs post-MI, we found the type I interferon (IFN) pathway significantly inhibited in HSC/multipotent progenitor subclusters and the absence of type I IFN signaling enhanced the MI-induced spleen EMH. Lipidomics analysis revealed that prostaglandin I2 (PGI2) was markedly reduced in the spleen. Mechanistically, PGI2 suppressed MI-induced EMH through a PGI2 receptor (IP)-cAMP-453p-SP1 cascade in spleen HSPCs. Finally, hematopoietic cell-specific IP-deficient mice exhibited enhanced EMH and improved cardiac recovery post-MI, which mitigated the adverse secondary outcomes of treatment with cicaprost, a PGI2 analog and anti-inflammatory agent. Conclusions: Together, our findings revealed that a PGI2–IFN axis was involved in spleen EMH after MI, providing new mechanistic insights into spleen EMH post-MI and offering a new therapeutic target for treating ischemic cardiac injury.","INSTITUTE":"Tianjin Medical University","LABORATORY":"Metabolic cardiovascular disease lab","LAST_NAME":"Lv","FIRST_NAME":"Huizhen","ADDRESS":"Qixiangtai Road 22th, Tianjin, Tianjin, 300070, China","EMAIL":"lvhuizhen@tmu.edu.cn","PHONE":"83336591"},

"STUDY":{"STUDY_TITLE":"Suppression of prostaglandin I2–type I interferon axis induces extramedullary hematopoiesis to promote cardiac repair after myocardial infarction","STUDY_SUMMARY":"Background: Immune cells are closely associated with all processes of cardiac repair following myocardial infarction (MI), including the initiation, development, and resolution of inflammation. Spleen extramedullary hematopoiesis (EMH) serves as a critical source of emergency mature blood cells that are generated through the self-renewal and differentiation of hematopoietic stem/progenitor cells (HSPCs). However, how EMH responds to MI and the role of EMH in cardiac repair post-MI remains unclear. Methods: To assess the role of spleen EMH in MI, a Tcf21CreERScfflox/flox MI mouse model with inhibited EMH was constructed. GFP+ HSCs sorted from eGFP mouse spleen by flow cytometry and injected into Tcf21CreERScfflox/flox mice to test the sources of local inflammatory cells during MI. Using highly specific liquid chromatography-tandem mass spectrometry and single-cell RNA sequencing, we analyzed the lipidomic profile of arachidonic acid metabolites and the transcriptomes of HSPCs in the spleen after MI. Results: We found that MI enhanced EMH, as reflected by the increase in spleen weight and volume and the number of HSPCs in the spleen. The lack of EMH in Scf-deficient mice exacerbated tissue injury post-MI. Analyzing the transcriptome of spleen HSPCs post-MI, we found the type I interferon (IFN) pathway significantly inhibited in HSC/multipotent progenitor subclusters and the absence of type I IFN signaling enhanced the MI-induced spleen EMH. Lipidomics analysis revealed that prostaglandin I2 (PGI2) was markedly reduced in the spleen. Mechanistically, PGI2 suppressed MI-induced EMH through a PGI2 receptor (IP)-cAMP-453p-SP1 cascade in spleen HSPCs. Finally, hematopoietic cell-specific IP-deficient mice exhibited enhanced EMH and improved cardiac recovery post-MI, which mitigated the adverse secondary outcomes of treatment with cicaprost, a PGI2 analog and anti-inflammatory agent. Conclusions: Together, our findings revealed that a PGI2–IFN axis was involved in spleen EMH after MI, providing new mechanistic insights into spleen EMH post-MI and offering a new therapeutic target for treating ischemic cardiac injury.","INSTITUTE":"Tianjin Medical University","LAST_NAME":"Lv","FIRST_NAME":"Huizhen","ADDRESS":"Qixiangtai Road 22th, Tianjin, Tianjin, 300070, China","EMAIL":"lvhuizhen@tmu.edu.cn","PHONE":"13212161520"},

"SUBJECT":{"SUBJECT_TYPE":"Mammal","SUBJECT_SPECIES":"Mus musculus","TAXONOMY_ID":"10090"},
"SUBJECT_SAMPLE_FACTORS":[
{
"Subject ID":"-",
"Sample ID":"Sham-1",
"Factors":{"Sample source":"Spleen","treatment":"Sham"},
"Additional sample data":{"RAW_FILE_NAME( raw data file names)":"Data_2_eico_lvhuizhen_48-1"}
},
{
"Subject ID":"-",
"Sample ID":"Sham-2",
"Factors":{"Sample source":"Spleen","treatment":"Sham"},
"Additional sample data":{"RAW_FILE_NAME( raw data file names)":"Data_2_eico_lvhuizhen_48-2"}
},
{
"Subject ID":"-",
"Sample ID":"Sham-3",
"Factors":{"Sample source":"Spleen","treatment":"Sham"},
"Additional sample data":{"RAW_FILE_NAME( raw data file names)":"Data_2_eico_lvhuizhen_48-3"}
},
{
"Subject ID":"-",
"Sample ID":"Sham-4",
"Factors":{"Sample source":"Spleen","treatment":"Sham"},
"Additional sample data":{"RAW_FILE_NAME( raw data file names)":"Data_2_eico_lvhuizhen_48-4"}
},
{
"Subject ID":"-",
"Sample ID":"Sham-5",
"Factors":{"Sample source":"Spleen","treatment":"Sham"},
"Additional sample data":{"RAW_FILE_NAME( raw data file names)":"Data_2_eico_lvhuizhen_48-5"}
},
{
"Subject ID":"-",
"Sample ID":"Sham-6",
"Factors":{"Sample source":"Spleen","treatment":"Sham"},
"Additional sample data":{"RAW_FILE_NAME( raw data file names)":"Data_2_eico_lvhuizhen_48-6"}
},
{
"Subject ID":"-",
"Sample ID":"Sham-7",
"Factors":{"Sample source":"Spleen","treatment":"Sham"},
"Additional sample data":{"RAW_FILE_NAME( raw data file names)":"Data_2_eico_lvhuizhen_48-7"}
},
{
"Subject ID":"-",
"Sample ID":"Sham-8",
"Factors":{"Sample source":"Spleen","treatment":"Sham"},
"Additional sample data":{"RAW_FILE_NAME( raw data file names)":"Data_2_eico_lvhuizhen_48-8"}
},
{
"Subject ID":"-",
"Sample ID":"Sham-9",
"Factors":{"Sample source":"Spleen","treatment":"Sham"},
"Additional sample data":{"RAW_FILE_NAME( raw data file names)":"Data_2_eico_lvhuizhen_48-9"}
},
{
"Subject ID":"-",
"Sample ID":"MI 1d-1",
"Factors":{"Sample source":"Spleen","treatment":"MI1d"},
"Additional sample data":{"RAW_FILE_NAME( raw data file names)":"Data_2_eico_lvhuizhen_48-10"}
},
{
"Subject ID":"-",
"Sample ID":"MI 1d-2",
"Factors":{"Sample source":"Spleen","treatment":"MI1d"},
"Additional sample data":{"RAW_FILE_NAME( raw data file names)":"Data_2_eico_lvhuizhen_48-11"}
},
{
"Subject ID":"-",
"Sample ID":"MI 1d-3",
"Factors":{"Sample source":"Spleen","treatment":"MI1d"},
"Additional sample data":{"RAW_FILE_NAME( raw data file names)":"Data_2_eico_lvhuizhen_48-12"}
},
{
"Subject ID":"-",
"Sample ID":"MI 1d-4",
"Factors":{"Sample source":"Spleen","treatment":"MI1d"},
"Additional sample data":{"RAW_FILE_NAME( raw data file names)":"Data_2_eico_lvhuizhen_48-13"}
},
{
"Subject ID":"-",
"Sample ID":"MI 1d-5",
"Factors":{"Sample source":"Spleen","treatment":"MI1d"},
"Additional sample data":{"RAW_FILE_NAME( raw data file names)":"Data_2_eico_lvhuizhen_48-14"}
},
{
"Subject ID":"-",
"Sample ID":"MI 1d-6",
"Factors":{"Sample source":"Spleen","treatment":"MI1d"},
"Additional sample data":{"RAW_FILE_NAME( raw data file names)":"Data_2_eico_lvhuizhen_48-15"}
},
{
"Subject ID":"-",
"Sample ID":"MI 1d-7",
"Factors":{"Sample source":"Spleen","treatment":"MI1d"},
"Additional sample data":{"RAW_FILE_NAME( raw data file names)":"Data_2_eico_lvhuizhen_48-16"}
},
{
"Subject ID":"-",
"Sample ID":"MI 1d-8",
"Factors":{"Sample source":"Spleen","treatment":"MI1d"},
"Additional sample data":{"RAW_FILE_NAME( raw data file names)":"Data_2_eico_lvhuizhen_48-17"}
},
{
"Subject ID":"-",
"Sample ID":"MI 1d-9",
"Factors":{"Sample source":"Spleen","treatment":"MI1d"},
"Additional sample data":{"RAW_FILE_NAME( raw data file names)":"Data_2_eico_lvhuizhen_48-18"}
},
{
"Subject ID":"-",
"Sample ID":"MI 3d-1",
"Factors":{"Sample source":"Spleen","treatment":"MI 3d"},
"Additional sample data":{"RAW_FILE_NAME( raw data file names)":"Data_2_eico_lvhuizhen_48-19"}
},
{
"Subject ID":"-",
"Sample ID":"MI 3d-2",
"Factors":{"Sample source":"Spleen","treatment":"MI 3d"},
"Additional sample data":{"RAW_FILE_NAME( raw data file names)":"Data_2_eico_lvhuizhen_48-20"}
},
{
"Subject ID":"-",
"Sample ID":"MI 3d-3",
"Factors":{"Sample source":"Spleen","treatment":"MI 3d"},
"Additional sample data":{"RAW_FILE_NAME( raw data file names)":"Data_2_eico_lvhuizhen_48-21"}
},
{
"Subject ID":"-",
"Sample ID":"MI 3d-4",
"Factors":{"Sample source":"Spleen","treatment":"MI 3d"},
"Additional sample data":{"RAW_FILE_NAME( raw data file names)":"Data_2_eico_lvhuizhen_48-22"}
},
{
"Subject ID":"-",
"Sample ID":"MI 3d-5",
"Factors":{"Sample source":"Spleen","treatment":"MI 3d"},
"Additional sample data":{"RAW_FILE_NAME( raw data file names)":"Data_2_eico_lvhuizhen_48-23"}
},
{
"Subject ID":"-",
"Sample ID":"MI 3d-6",
"Factors":{"Sample source":"Spleen","treatment":"MI 3d"},
"Additional sample data":{"RAW_FILE_NAME( raw data file names)":"Data_2_eico_lvhuizhen_48-24"}
},
{
"Subject ID":"-",
"Sample ID":"MI 3d-7",
"Factors":{"Sample source":"Spleen","treatment":"MI 3d"},
"Additional sample data":{"RAW_FILE_NAME( raw data file names)":"Data_2_eico_lvhuizhen_48-25"}
},
{
"Subject ID":"-",
"Sample ID":"MI 3d-8",
"Factors":{"Sample source":"Spleen","treatment":"MI 3d"},
"Additional sample data":{"RAW_FILE_NAME( raw data file names)":"Data_2_eico_lvhuizhen_48-26"}
},
{
"Subject ID":"-",
"Sample ID":"MI 3d-9",
"Factors":{"Sample source":"Spleen","treatment":"MI 3d"},
"Additional sample data":{"RAW_FILE_NAME( raw data file names)":"Data_2_eico_lvhuizhen_48-27"}
}
],
"COLLECTION":{"COLLECTION_SUMMARY":"Spleen samples from mice subjected to myocardial infarction (MI) surgery were extracted with liquid–liquid extraction.","SAMPLE_TYPE":"Spleen","STORAGE_CONDITIONS":"-80℃"},

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

"SAMPLEPREP":{"SAMPLEPREP_SUMMARY":"50 mg of spleen tissues was homogenized with methanol (2% formic acid and 0.01 mol/L BHT) spiked with internal standard mixture. After centrifugation, the supernatant was added to water and ethylacetate, and the sample was mixed and centrifuged at 12,000 × g. The upper organic phase was transferred to a new tube, and the water phase was extracted again. The organic phase was combined and then evaporated to dryness and further dissolved in 100 μL of 30% acetonitrile. After vigorous mixing, samples were filtered by use of centrifuge tube filters (nylon membrane, 0.22 μm)."},

"CHROMATOGRAPHY":{"CHROMATOGRAPHY_TYPE":"Reversed phase","INSTRUMENT_NAME":"Waters Acquity","COLUMN_NAME":"Waters ACQUITY UPLC BEH C18 (50 x 2.1mm,1.7um)","SOLVENT_A":"100% water; 0.3% ethanoic acid","SOLVENT_B":"100% acetonitrile","FLOW_GRADIENT":"0-3min：70%A:30%B，3-20min：40%A:60%B, 20-27min：20%A:80%B，27-30min：70%A;30%B","FLOW_RATE":"0.25mL/min","COLUMN_TEMPERATURE":"25"},

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

"MS":{"INSTRUMENT_NAME":"ABI Sciex 5500 QTrap","INSTRUMENT_TYPE":"QTRAP","MS_TYPE":"ESI","ION_MODE":"NEGATIVE","MS_COMMENTS":"Arachidonic acid metabolites were quantified by use of a 5500 QTRAP hybrid triple quadrupole linear ion trap mass spectrometer (AB Sciex, Foster City, CA, USA) equipped with a Turbo Ion Spray electrospray ionization source. The mass spectrometer was operated using the software Analyst 1.5.1. Analytes were detected using multiple reaction monitoring (MRM) scans in negative mode. The dwell time used for all MRM experiments was 25 ms. The ion source parameters were set as follows: CUR  =  40 psi, GS1  =  30 psi, GS2  =  30 psi, IS  =  −4500 V, CAD  =  medium, and temp  =  500°C. Metaboanalyst 3.0 (http://www.metaboanalyst.ca) was used for metabolomic data analysis."},

"MS_METABOLITE_DATA":{
"Units":"ng/mg of tissue",

"Data":[{"Metabolite":"AA_COX_6k-PGF1a","Sham-1":"1.05","Sham-2":"1.14","Sham-3":"1.16","Sham-4":"1.20","Sham-5":"1.25","Sham-6":"1.42","Sham-7":"1.52","Sham-8":"1.57","Sham-9":"1.97","MI 1d-1":"0.25","MI 1d-2":"1.16","MI 1d-3":"1.24","MI 1d-4":"0.25","MI 1d-5":"1.25","MI 1d-6":"1.26","MI 1d-7":"1.28","MI 1d-8":"1.43","MI 1d-9":"0.16","MI 3d-1":"0.08","MI 3d-2":"0.66","MI 3d-3":"0.78","MI 3d-4":"0.07","MI 3d-5":"0.06","MI 3d-6":"0.92","MI 3d-7":"0.94","MI 3d-8":"0.94","MI 3d-9":"1.01"},{"Metabolite":"AA_COX_PGD2","Sham-1":"2.67","Sham-2":"2.02","Sham-3":"2.65","Sham-4":"2.01","Sham-5":"2.69","Sham-6":"2.66","Sham-7":"2.35","Sham-8":"3.20","Sham-9":"2.43","MI 1d-1":"0.86","MI 1d-2":"2.60","MI 1d-3":"2.63","MI 1d-4":"0.71","MI 1d-5":"2.78","MI 1d-6":"2.49","MI 1d-7":"2.91","MI 1d-8":"2.55","MI 1d-9":"0.43","MI 3d-1":"0.12","MI 3d-2":"1.55","MI 3d-3":"1.55","MI 3d-4":"0.22","MI 3d-5":"0.14","MI 3d-6":"2.06","MI 3d-7":"2.31","MI 3d-8":"1.99","MI 3d-9":"2.62"},{"Metabolite":"AA_COX_15d-PGJ2","Sham-1":"0.00","Sham-2":"0.00","Sham-3":"0.00","Sham-4":"0.00","Sham-5":"0.00","Sham-6":"0.00","Sham-7":"0.00","Sham-8":"0.00","Sham-9":"0.00","MI 1d-1":"0.00","MI 1d-2":"0.00","MI 1d-3":"0.00","MI 1d-4":"0.00","MI 1d-5":"0.00","MI 1d-6":"0.00","MI 1d-7":"0.00","MI 1d-8":"0.00","MI 1d-9":"0.00","MI 3d-1":"0.00","MI 3d-2":"0.00","MI 3d-3":"0.00","MI 3d-4":"0.00","MI 3d-5":"0.00","MI 3d-6":"0.00","MI 3d-7":"0.00","MI 3d-8":"0.00","MI 3d-9":"0.00"},{"Metabolite":"AA_COX_PGB2","Sham-1":"0.00","Sham-2":"0.00","Sham-3":"0.00","Sham-4":"0.00","Sham-5":"0.00","Sham-6":"0.00","Sham-7":"0.00","Sham-8":"0.00","Sham-9":"0.00","MI 1d-1":"0.00","MI 1d-2":"0.00","MI 1d-3":"0.00","MI 1d-4":"0.00","MI 1d-5":"0.00","MI 1d-6":"0.00","MI 1d-7":"0.00","MI 1d-8":"0.00","MI 1d-9":"0.00","MI 3d-1":"0.00","MI 3d-2":"0.00","MI 3d-3":"0.00","MI 3d-4":"0.00","MI 3d-5":"0.00","MI 3d-6":"0.00","MI 3d-7":"0.00","MI 3d-8":"0.00","MI 3d-9":"0.00"},{"Metabolite":"AA_COX_PGE2","Sham-1":"0.51","Sham-2":"0.54","Sham-3":"0.62","Sham-4":"0.49","Sham-5":"0.68","Sham-6":"0.39","Sham-7":"0.58","Sham-8":"0.80","Sham-9":"0.71","MI 1d-1":"0.12","MI 1d-2":"0.64","MI 1d-3":"0.63","MI 1d-4":"0.10","MI 1d-5":"0.62","MI 1d-6":"0.62","MI 1d-7":"0.68","MI 1d-8":"0.65","MI 1d-9":"0.06","MI 3d-1":"0.02","MI 3d-2":"0.24","MI 3d-3":"0.30","MI 3d-4":"0.03","MI 3d-5":"0.02","MI 3d-6":"0.44","MI 3d-7":"0.40","MI 3d-8":"0.34","MI 3d-9":"0.55"},{"Metabolite":"AA_COX_PGF2a","Sham-1":"0.06","Sham-2":"0.06","Sham-3":"0.08","Sham-4":"0.05","Sham-5":"0.08","Sham-6":"0.06","Sham-7":"0.06","Sham-8":"0.10","Sham-9":"0.06","MI 1d-1":"0.01","MI 1d-2":"0.09","MI 1d-3":"0.07","MI 1d-4":"0.02","MI 1d-5":"0.08","MI 1d-6":"0.08","MI 1d-7":"0.07","MI 1d-8":"0.07","MI 1d-9":"0.01","MI 3d-1":"0.00","MI 3d-2":"0.05","MI 3d-3":"0.04","MI 3d-4":"0.00","MI 3d-5":"0.00","MI 3d-6":"0.09","MI 3d-7":"0.05","MI 3d-8":"0.04","MI 3d-9":"0.06"},{"Metabolite":"AA_COX_PGJ2","Sham-1":"0.03","Sham-2":"0.03","Sham-3":"0.02","Sham-4":"0.02","Sham-5":"0.04","Sham-6":"0.02","Sham-7":"0.02","Sham-8":"0.06","Sham-9":"0.02","MI 1d-1":"0.00","MI 1d-2":"0.04","MI 1d-3":"0.04","MI 1d-4":"0.00","MI 1d-5":"0.03","MI 1d-6":"0.02","MI 1d-7":"0.04","MI 1d-8":"0.02","MI 1d-9":"0.00","MI 3d-1":"0.00","MI 3d-2":"0.01","MI 3d-3":"0.01","MI 3d-4":"0.00","MI 3d-5":"0.00","MI 3d-6":"0.02","MI 3d-7":"0.02","MI 3d-8":"0.01","MI 3d-9":"0.04"},{"Metabolite":"AA_COX_TXB2","Sham-1":"0.23","Sham-2":"0.22","Sham-3":"0.28","Sham-4":"0.21","Sham-5":"0.27","Sham-6":"0.23","Sham-7":"0.24","Sham-8":"0.31","Sham-9":"0.24","MI 1d-1":"0.06","MI 1d-2":"0.28","MI 1d-3":"0.27","MI 1d-4":"0.06","MI 1d-5":"0.28","MI 1d-6":"0.27","MI 1d-7":"0.31","MI 1d-8":"0.29","MI 1d-9":"0.03","MI 3d-1":"0.01","MI 3d-2":"0.16","MI 3d-3":"0.18","MI 3d-4":"0.02","MI 3d-5":"0.01","MI 3d-6":"0.22","MI 3d-7":"0.21","MI 3d-8":"0.23","MI 3d-9":"0.25"},{"Metabolite":"AA_LOX_11-HETE","Sham-1":"1.04","Sham-2":"0.92","Sham-3":"0.82","Sham-4":"0.83","Sham-5":"1.13","Sham-6":"0.96","Sham-7":"1.11","Sham-8":"1.21","Sham-9":"1.27","MI 1d-1":"0.15","MI 1d-2":"1.11","MI 1d-3":"1.18","MI 1d-4":"0.17","MI 1d-5":"1.29","MI 1d-6":"1.52","MI 1d-7":"1.36","MI 1d-8":"1.14","MI 1d-9":"0.10","MI 3d-1":"0.03","MI 3d-2":"0.46","MI 3d-3":"0.43","MI 3d-4":"0.04","MI 3d-5":"0.04","MI 3d-6":"0.86","MI 3d-7":"0.85","MI 3d-8":"0.59","MI 3d-9":"1.15"},{"Metabolite":"AA_LOX_12-HETE","Sham-1":"3.87","Sham-2":"11.80","Sham-3":"12.50","Sham-4":"4.25","Sham-5":"13.59","Sham-6":"12.49","Sham-7":"10.30","Sham-8":"9.74","Sham-9":"3.34","MI 1d-1":"0.55","MI 1d-2":"24.46","MI 1d-3":"6.23","MI 1d-4":"0.63","MI 1d-5":"5.11","MI 1d-6":"8.95","MI 1d-7":"5.74","MI 1d-8":"6.51","MI 1d-9":"0.43","MI 3d-1":"0.14","MI 3d-2":"1.72","MI 3d-3":"5.30","MI 3d-4":"0.12","MI 3d-5":"0.10","MI 3d-6":"15.58","MI 3d-7":"6.73","MI 3d-8":"6.27","MI 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}