Academic Journal
Integrated transcriptomic analysis reveals lymphatic Icam1-mediated immune dynamics after myocardial infarction.
| Τίτλος: | Integrated transcriptomic analysis reveals lymphatic Icam1-mediated immune dynamics after myocardial infarction. |
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| Συγγραφείς: | Chen XT; College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China.; BGI Research, Shenzhen, Guangdong 518083, China., Hu BB; Pediatric Translational Medicine Institute and Pediatric Congenital Heart Disease Institute, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China., Zhang Z; College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China.; BGI Research, Shenzhen, Guangdong 518083, China., Chen ZX; Pediatric Translational Medicine Institute and Pediatric Congenital Heart Disease Institute, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China., Chen SL; College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China.; BGI Research, Shenzhen, Guangdong 518083, China., Su SX; College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China.; BGI Research, Shenzhen, Guangdong 518083, China., Zhang Z; Department of Cardiology, Zhuhai People's Hospital (Zhuhai Hospital Affiliated with Jinan University), Zhuhai, Guangdong 519000, China., Huang C; Department of Cardiology, Fuwai Yunnan Cardiovascular Hospital, Cardiovascular Hospital Affiliated to Kunming Medical University, Kunming, Yunnan 650000, China., Wang L; Department of Cardiovascular Medicine, Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510120, China., Lai KS; Pediatric Translational Medicine Institute and Pediatric Congenital Heart Disease Institute, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China., Yang JJ; Pediatric Translational Medicine Institute and Pediatric Congenital Heart Disease Institute, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China., Wang Y; Pediatric Translational Medicine Institute and Pediatric Congenital Heart Disease Institute, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China., Fang XD; BGI Research, Sanya, Hainan 572025, China., Zhang Z; Pediatric Translational Medicine Institute and Pediatric Congenital Heart Disease Institute, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.; Shanghai Collaborative Innovative Center of Intelligent Medical Device and Active Health, Shanghai University of Medicine & Health Sciences, Shanghai 201318, China.; Core Research Laboratory, Fujian Children's Hospital, Fuzhou, Fujian 350012, China.; Department of Hainan Key Laboratory of Molecular Medicine for Women and Children's Health, Shanghai Children's Medical Center Hainan Branch, Shanghai Jiao Tong University School of Medicine, Sanya, Hainan 572000, China., Shen J; BGI Research, Shenzhen, Guangdong 518083, China. E-mail: juan.shen@genomics.cn., Zhang M; Pediatric Translational Medicine Institute and Pediatric Congenital Heart Disease Institute, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China. E-mail: minzhang5099@gmail.com. |
| Πηγή: | Zoological research [Zool Res] 2026 May 18; Vol. 47 (3), pp. 691-705. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Science Press Country of Publication: China NLM ID: 101697192 Publication Model: Print Cited Medium: Internet ISSN: 2095-8137 (Print) Linking ISSN: 20958137 NLM ISO Abbreviation: Zool Res Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Beijing, China : Science Press, 2016- |
| Ιατρικοί όροι (MeSH): | Myocardial Infarction*/immunology , Myocardial Infarction*/metabolism , Intercellular Adhesion Molecule-1*/genetics , Intercellular Adhesion Molecule-1*/metabolism , Lymphatic Vessels*/metabolism, Endothelial Cells/metabolism ; Animals ; Mice ; Gene Expression Profiling ; Gene Expression Regulation ; Mice, Knockout ; Male |
| Περίληψη: | Cardiac lymphatic vessels are active regulators of immune surveillance and inflammatory resolution after myocardial injury. Intercellular adhesion molecule-1 (ICAM-1), a cell-surface glycoprotein broadly expressed in endothelial cells, mediates leukocyte adhesion and trafficking during inflammation; however, how Icam1 in lymphatic endothelial cells (LECs) shapes the post-infarction immune microenvironment remains unclear. In this study, an LEC-specific Icam1 conditional knockout ( Icam1cko) model was generated, and single-cell RNA sequencing and spatial transcriptomics were applied to characterize cellular and molecular remodeling at 3, 7, 21, and 42 days post-myocardial infarction (MI). Results showed that loss of Icam1 in LECs increased post-MI inflammation and fibrotic remodeling, indicating aggravated cardiac injury. Integrated transcriptomic analyses revealed broad alterations in cell composition and cell type-specific molecular signatures in the Icam1cko group, with prominent expansion and activation of proinflammatory neutrophil and macrophage subsets. Cell-cell communication analysis indicated that LEC-specific Icam1 deletion disrupted ICAM-dependent immune cell trafficking through lymphatic vessels, thereby impairing inflammatory cell clearance. Accumulated proinflammatory populations further reinforced leukocyte recruitment through CXCL-mediated crosstalk, amplifying immune imbalance within the infarcted myocardium. Collectively, these findings indicate that LEC Icam1 might be a potential therapeutic target for improving post-MI outcomes. |
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| Contributed Indexing: | Keywords: Icam1; Lymphatic endothelial cells; Myocardial infarction; Single-cell RNA sequencing; Spatial transcriptomic sequencing Local Abstract: [Publisher, Chinese] 心脏淋巴管在损伤后可主动调节免疫反应。细胞间黏附分子-1（ICAM-1）是一种细胞表面糖蛋白，广泛表达于内皮细胞中，并通过调控免疫细胞从循环系统的募集参与炎症过程。然而，淋巴内皮细胞（LECs）中 Icam1在调控心肌梗死（MI）相关免疫微环境中的具体作用尚不清楚。该研究构建了LEC特异性的 Icam1条件性敲除（ Icam1cko）小鼠模型，并在心梗后第3、7、21和42天分别进行了单细胞转录组和空间转录组测序，以评估心脏组织的细胞动态特征。研究结果表明，LECs中 Icam1的缺失导致炎症和纤维化程度增加，提示心脏损伤加重。我们观察到 Icam1cko组在细胞类型比例及分子特征方面均发生显著变化。值得注意的是， Icam1cko组中促炎性中性粒细胞和巨噬细胞亚群的激活是其关键特征。细胞互作分析显示， Icam1的敲除可能通过LEC特异性的ICAM信号阻碍免疫细胞的引流。此外，累积的促炎细胞群体通过CXCL信号进一步吸引更多免疫细胞，最终加剧了 Icam1cko心脏中的免疫微环境破坏。综上，我们的研究提示LEC来源的 Icam1可能是改善心梗后预后的潜在治疗靶点。. |
| Molecular Sequence: | GEO GSE308860 |
| Substance Nomenclature: | 126547-89-5 (Intercellular Adhesion Molecule-1) 0 (Icam1 protein, mouse) |
| Entry Date(s): | Date Created: 20260604 Date Completed: 20260609 Latest Revision: 20261010 |
| Update Code: | 20261010 |
| PubMed Central ID: | PMC13647053 |
| DOI: | 10.24272/j.issn.2095-8137.2025.222 |
| PMID: | 42237943 |
| Βάση Δεδομένων: | MEDLINE |
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