Hu Beibei, Liu Xiangyang, Xiong Shanshan, Gong Qin, Yang Junjie, Shi Hongjun, Zhang Min, Liang Fei, Zhang Zhen
Pediatric Translational Medicine Institute and Pediatric Congenital Heart Disease Institute, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
School of Medicine, Westlake University, Hangzhou, Zhejiang, China.
Front Genet. 2025 Jan 15;15:1525931. doi: 10.3389/fgene.2024.1525931. eCollection 2024.
Macrophages are known to support cardiac development and homeostasis, contributing to tissue remodeling and repair in the adult heart. However, it remains unclear whether embryonic macrophages also respond to abnormalities in the developing heart. Previously, we reported that the structural protein Sorbs2 promotes the development of the second heart field, with its deficiency resulting in atrial septal defects (ASD). In analyzing RNA-seq data, we noted an upregulation of macrophage-related genes in hearts. Immunostaining and lineage-tracing confirmed an increase in macrophage numbers, underscoring a macrophage response to myocardial abnormalities. Partial depletion of macrophages led to downregulation of genes involved in lipid metabolism, muscle development and organ regeneration, alongside upregulation of genes associated with DNA damage-induced senescence and cardiomyopathy. Additionally, a non-significant increase in septal defects in macrophage-depleted hearts suggests a potential reparative function for macrophages in maintaining structural integrity. Valve formation, however, remained unaffected. Our findings suggest that embryonic macrophages might sense abnormalities in embryonic cardiomyocytes and could adaptively support cardiac structure and function development in response to myocardial abnormalities.
已知巨噬细胞可支持心脏发育和稳态，有助于成年心脏的组织重塑和修复。然而，尚不清楚胚胎巨噬细胞是否也会对发育中心脏的异常情况做出反应。此前，我们报道结构蛋白Sorbs2促进第二心脏场的发育，其缺乏会导致房间隔缺损（ASD）。在分析RNA测序数据时，我们注意到心脏中巨噬细胞相关基因的上调。免疫染色和谱系追踪证实巨噬细胞数量增加，突出了巨噬细胞对心肌异常的反应。巨噬细胞部分耗竭导致参与脂质代谢、肌肉发育和器官再生的基因下调，同时与DNA损伤诱导的衰老和心肌病相关的基因上调。此外，巨噬细胞耗竭的心脏中房间隔缺损有不显著增加，提示巨噬细胞在维持结构完整性方面可能具有修复功能。然而，瓣膜形成未受影响。我们的研究结果表明，胚胎巨噬细胞可能感知胚胎心肌细胞中的异常情况，并可响应心肌异常情况适应性地支持心脏结构和功能发育。
