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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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℃ |
