Summary of project PR002014
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
| 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 |
Summary of all studies in project PR002014
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST003244 | Suppression of prostaglandin I2–type I interferon axis induces extramedullary hematopoiesis to promote cardiac repair after myocardial infarction | Mus musculus | Tianjin Medical University | MS | 2024-07-01 | 1 | 27 | Uploaded data (5M)* |
