Download This Paper
Preprints with The Lancet is a collaboration between The Lancet Group of journals and SSRN to facilitate the open sharing of preprints for early engagement, community comment, and collaboration. Preprints available here are not Lancet publications or necessarily under review with a Lancet journal. These preprints are early-stage research papers that have not been peer-reviewed. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. The findings should not be used for clinical or public health decision-making or presented without highlighting these facts. For more information, please see the FAQs.
Deciphering Phenotype-Specific Macrophages in Aortic Dissection by Integrating Single-Cell and Bulk RNA Sequencing Analysis
26 Pages Posted: 2 Dec 2022
More...Abstract
Background: Aortic dissection (AD) is one of the most lethal cardiovascular diseases and is primarily characterised by phenotypic switching of various cell types with heterogeneous origins in the aortic wall. This study aimed to investigate the most disease-relevant cell populations and their molecular characteristics as potential therapeutic targets in the pathogenesis of AD.
Methods: Single-cell RNA sequencing (scRNA-seq) analysis was performed on 47,303 cells from six participants to uncover the landscape of cell populations in AD. Phenotype-specific cell subpopulations and molecular signatures were investigated by integrating single-cell transcriptomes with publicly accessible bulk gene expression profiles.
Findings: Our study provides a comprehensive landscape of the microenvironment in the dissected aorta and its normal counterpart at single-cell resolution. We uncovered five major macrophage populations in the aorta and established their gene expression signatures. Integrating bulk and scRNA-seq data yielded a subset of phenotype-specific macrophages that expressed a high level of CXCL3. Importantly, phenotype-specific macrophages were demonstrated to promote neutrophil activation, chemotaxis, and degranulation through the CXCL3/CXCR2 axis, which may further perpetuate inflammation and deteriorate the immune microenvironment during AD pathogenesis.
Interpretation: Inflammatory and atherosclerosis-like macrophages are phenotype-specific and the most disease-relevant cell populations in AD, which may aggravate the disease through promoting neutrophil activation, chemotaxis, and degranulation through the CXCL3/CXCR2 axis.
Funding Information: This work was supported by the National Natural Science Foundation of China (grant number: 81970412), Science and Technology Innovation Plan of Shanghai Science and Technology Commission (grant number: 18441902400), Xiamen Municipal Health Science and Technology Program Fund (grant number: 3502Z20194034).
Declaration of Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Ethics Approval Statement: This study was approved by the Ethics Committee of Zhongshan Hospital of Fudan University (IRB number B2019-231R). Healthy normal aortas and dissected aortas were collected from participants with informed written consent, and under approval of local medical ethnics from Zhongshan Hospital Fudan University.
Keywords: phenotype, macrophages, neutrophil, inflammation, aortic dissection
Suggested Citation: Suggested Citation