Dataset Information

Transcriptomic profiling of Adcy7-knockout bone marrow-derived macrophages

ABSTRACT: Myocardial ischemia/reperfusion (I/R) injury remarkably thwarts the therapeutic efficiency of percutaneous coronary intervention for myocardial ischemia disorders, and cardiac macrophages have been shown to play critical roles during the injury process. Here, we identified adenylyl cyclase 7 (ADCY7) in macrophage as a critical candidate for I/R injury based on spatial transcriptomics analysis and multi-parameter flow cytometry and confirmed the expression changes in I/R injury mouse model and patients with myocardial infarction. Taking advantage of depletion/reconstitution of macrophages in male mice, we demonstrated that macrophage Adcy7 deficiency significantly exacerbated myocardial I/R injury and impaired cardiac function, while Adcy7 overexpression attenuated these pathological manifestations. Notably, we observed that macrophage Adcy7 deficiency led to more infiltration of leukocytes and production of pro-inflammatory cytokines. To gain insight into how ADCY7 regulates inflammation, we performed transcriptomic and phosphor-proteomic analysis on Adcy7-deficient bone marrow-derived macrophages, and found that ADCY7 induced protein kinase A activation, leading to inhibition of nuclear translocation of NF-κB, thus restraining pro-inflammatory response. We further developed photoactivated adenylyl cyclase activation system combined with the macrophage depletion/reconstitution procedure and achieved substantial effect to alleviate cardiac inflammation and myocardial I/R injury. Together, our study identified ADCY7 as a promising therapeutic target for developing effective anti-inflammatory strategy to ameliorate myocardial I/R injury.

ORGANISM(S): Mus musculus

PROVIDER: GSE311668 | GEO | 2025/12/01

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Background: Sepsis can lead to multiple organ damage, and the heart is one of the most vulnerable organs. Vagal nerve stimulation can reduce myocardial injury in sepsis and improve survival rate. However, the relative effect of disparate cell populations on sepsis induced myocardial dysfunction and the low-level tragus stimulation on it, remain unclear. Methods: We used the cardiac single-cell transcriptomic strategy to characterize the cardiac cell population and the network of cells that forms the heart. And we selected all cardiac macrophage from CD45+ cells using single-cell mRNA sequencing data. Then we used echocardiography performing, western blot and immunofluorescence and immunohistochemical technology to verify the data of the single-cell mRNA sequencing results. Results: In single-cell mRNA sequencing data, our analysis provides a comprehensive map of the cardiac cellular landscape uncovering multiple cell populations that contribute to sepsis induced myocardial dysfunction under low-level tragus stimulation. Pseudo timing analysis in single-cell sequencing showed that low level vagal nerve stimulation could induce the transformation of cardiac monocytes into M2 macrophages and play an anti-inflammatory role. After low-level tragus stimulation, the expression of α7nAChR in the heart tissue increased significantly. Echocardiography showed that low-level tragus stimulation could improve the cardiac function of septic myocardial injury of the mice. Comparing with the sepsis group, the expression of interleukin-1β in heart tissue of the mice in sepsis with low-level tragus stimulation group is significantly lower. Conclusion: Low-level tragus stimulation can improve sepsis-induced myocardial dysfunction by promoting cardiac monocytes to M2 macrophages. Goal of the study: In the present study, we aimed to screen macrophages, their crosstalk with other cells, and macrophages associated with cardiac injury and further verify their origins and roles in the septic myocardial injury process and low-level tragus stimulation (LL-TS) to treat septic myocardial dysfunction.

Dataset Information

Transcriptomic profiling of Adcy7-knockout bone marrow-derived macrophages

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets