Summary of Study ST003244
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 PR002014. The data can be accessed directly via it's Project DOI: 10.21228/M88R67 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.
| Study ID | ST003244 |
| 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 |
| lvhuizhen@tmu.edu.cn | |
| Phone | 13212161520 |
| Submit Date | 2024-02-25 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzML |
| Analysis Type Detail | LC-MS |
| Release Date | 2024-07-01 |
| Release Version | 1 |
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Project:
| Project ID: | PR002014 |
| Project DOI: | doi: 10.21228/M88R67 |
| 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 |
Subject:
| Subject ID: | SU003363 |
| Subject Type: | Mammal |
| Subject Species: | Mus musculus |
| Taxonomy ID: | 10090 |
| Species Group: | Mammals |
Factors:
Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)
| mb_sample_id | local_sample_id | treatment |
|---|---|---|
| SA353387 | MI 1d-7 | MI1d |
| SA353388 | MI 1d-9 | MI1d |
| SA353389 | MI 1d-8 | MI1d |
| SA353390 | MI 1d-6 | MI1d |
| SA353391 | MI 1d-5 | MI1d |
| SA353392 | MI 1d-4 | MI1d |
| SA353393 | MI 1d-3 | MI1d |
| SA353394 | MI 1d-2 | MI1d |
| SA353395 | MI 1d-1 | MI1d |
| SA353378 | MI 3d-9 | MI 3d |
| SA353379 | MI 3d-8 | MI 3d |
| SA353380 | MI 3d-7 | MI 3d |
| SA353381 | MI 3d-6 | MI 3d |
| SA353382 | MI 3d-5 | MI 3d |
| SA353383 | MI 3d-4 | MI 3d |
| SA353384 | MI 3d-3 | MI 3d |
| SA353385 | MI 3d-2 | MI 3d |
| SA353386 | MI 3d-1 | MI 3d |
| SA353396 | Sham-2 | Sham |
| SA353397 | Sham-9 | Sham |
| SA353398 | Sham-8 | Sham |
| SA353399 | Sham-7 | Sham |
| SA353400 | Sham-6 | Sham |
| SA353401 | Sham-5 | Sham |
| SA353402 | Sham-4 | Sham |
| SA353403 | Sham-3 | Sham |
| SA353404 | Sham-1 | Sham |
| Showing results 1 to 27 of 27 |
Collection:
| Collection ID: | CO003356 |
| 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 ID: | TR003372 |
| Treatment Summary: | No treatment |
Sample Preparation:
| Sampleprep ID: | SP003370 |
| 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 ID: | CH004018 |
| Instrument Name: | Waters Acquity |
| Column Name: | Waters ACQUITY UPLC BEH C18 (50 x 2.1mm,1.7um) |
| Column Temperature: | 25 |
| 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 |
| Solvent A: | 100% water; 0.3% ethanoic acid |
| Solvent B: | 100% acetonitrile |
| Chromatography Type: | Reversed phase |
Analysis:
| Analysis ID: | AN005314 |
| Analysis Type: | MS |
| Chromatography ID: | CH004018 |
| Num Factors: | 3 |
| Num Metabolites: | 25 |
| Units: | ng/mg of tissue |
