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 |
Select appropriate tab below to view additional metadata details:
Combined analysis:
| Analysis ID | AN005314 |
|---|---|
| Analysis type | MS |
| Chromatography type | Reversed phase |
| Chromatography system | Waters Acquity |
| Column | Waters ACQUITY UPLC BEH C18 (50 x 2.1mm,1.7um) |
| MS Type | ESI |
| MS instrument type | QTRAP |
| MS instrument name | ABI Sciex 5500 QTrap |
| Ion Mode | NEGATIVE |
| Units | ng/mg of tissue |
MS:
| MS ID: | MS005044 |
| Analysis ID: | AN005314 |
| Instrument Name: | ABI Sciex 5500 QTrap |
| Instrument Type: | QTRAP |
| MS Type: | ESI |
| 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. |
| Ion Mode: | NEGATIVE |
