Baotong Zhang , Wenbin Ji , Duowei Wang , Guoshan Chen , Wenhao Xiong , Feng Qi
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Abstract
Background and objective
Organ transplantation is a vital treatment for patients with end-stage organ diseases, and macrophages play a key role in the rejection process. This study seeks to pinpoint key genes responsible for the dynamic changes in macrophages during rejection and to evaluate their impact on macrophage polarization through bioinformatics analysis.
Methods
We selected single-cell sequencing data of mouse heart transplant models from Genome Sequence Archive to construct a dynamic landscape of immune cells during acute rejection. Key genes involved in macrophage changes were screened using pseudotime analysis and hdWGCNA. The mouse heart transplant models also were established to validate changes of the key genes during rejection.
Results
Bioinformatics analysis identified Gbp2 as the key gene driving macrophage dynamics during rejection, which was also confirmed in another dataset showed Gbp2 levels increased in macrophages during acute rejection. Further experiments validated the upregulation of Gbp2 in both tissues and macrophages during acute rejection, and in vitro experiments confirmed Gbp2 increasing in M1 macrophages.
Conclusion
Gbp2 is a key gene that regulates macrophage polarization during acute rejection, making it a potential therapeutic target for the acute rejection.
期刊介绍：
Tissue and Cell is devoted to original research on the organization of cells, subcellular and extracellular components at all levels, including the grouping and interrelations of cells in tissues and organs. The journal encourages submission of ultrastructural studies that provide novel insights into structure, function and physiology of cells and tissues, in health and disease. Bioengineering and stem cells studies focused on the description of morphological and/or histological data are also welcomed.
Studies investigating the effect of compounds and/or substances on structure of cells and tissues are generally outside the scope of this journal. For consideration, studies should contain a clear rationale on the use of (a) given substance(s), have a compelling morphological and structural focus and present novel incremental findings from previous literature.
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