数字农科院2.0

Single-nucleus transcriptomics reveal cardiac cell type-specific diversification in metabolic disease transgenic pigs

文献类型： 外文期刊

作者： Jiakun Miao;Kaiyi Zhang;Yu Yang;Shuang Xu;Juan Du;Tianwen Wu;Cong Tao;Yanfang Wang;Shulin Yang

作者机构：

关键词： Animals;Integrative aspects of cell biology;Model organism;Porcine cardiology;Transcriptomics

期刊名称： iScience

ISSN： 2589-0042

年卷期： 2024 年 27 卷 6 期

页码：

收录情况： SCIE（2024版）

摘要： Cardiac damage is widely present in patients with metabolic diseases, but the exact pathophysiological mechanisms involved remain unclear. The porcine heart is an ideal material for cardiovascular research due to its similarities to the human heart. This study evaluated pathological features and performed single-nucleus RNA sequencing (snRNA-seq) on myocardial samples from both wild-type and metabolic disease-susceptible transgenic pigs (previously established). We found that transgenic pigs exhibited lipid metabolism disturbances and myocardial injury after a high-fat high-sucrose diet intervention. snRNA-seq reveals the cellular landscape of healthy and metabolically disturbed pig hearts and identifies the major cardiac cell populations affected by metabolic diseases. Within metabolic disorder hearts, metabolically active cardiomyocytes exhibited impaired function and reduced abundance. Moreover, massive numbers of reparative LYVE1+ macrophages were lost. Additionally, proinflammatory endothelial cells were activated with high expression of multiple proinflammatory cytokines. Our findings provide insights into the cellular mechanisms of metabolic disease-induced myocardial injury.

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