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Identification of cell-to-cell interactions by ligand-receptor pairs in human fetal heart.
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease ( IF 6.2 ) Pub Date : 2020-08-12 , DOI: 10.1016/j.bbadis.2020.165917
Li Zhang 1 , Xin Shi 2 , Chang Gu 3 , Bo Chen 4 , Ming Wang 5 , Yu Yu 6 , Kun Sun 4 , Riquan Zhang 1
Affiliation  

The heart is the first organ to form during embryogenesis and its development is a complex process. In this study, we identified 120 ligand-receptor pairs including 65 ligands and 58 receptors specifically expressed in one of the nine cell types. The correlation analysis of the cell proportions revealed that the cell-to-cell contact exhibited spatial patterns in human fetal heart. Specifically, the cardiomyocytes (CMs) proportion might have negative correlation with proportion of endothelial cell in left atrium and ventricle during the heart development. In contrast, fibroblast-like cells and macrophages were jointly increased with the gestation. Furthermore, the ligand in CM, NPPA (Natriuretic Peptide A), and receptor in endothelial cell (EC), NPR3 (Natriuretic Peptide Receptor 3), were specifically expressed in atrial CM and endocardial cells, respectively, indicating that the atrial CM might communicate with endocardial cells via NPPA-NRP3 interaction. Moreover, the interplay between fibroblast-like cell and macrophage was observed in both left and right atriums via the ligand-receptor interactions of COL1A1/COL1A2 (Collagen Type I Alpha 1/2 Chain)-CD36 and CTGF (connective tissue growth factor)-ITGB2 (Integrin Subunit Beta 2). Functional enrichment analysis revealed that the ligand-receptor interactions might be associated with the intracellular activation of cGMP-PKG signaling pathway in ECs, PDGF-beta signaling pathway in fibroblast-like cell, and Toll-like receptor signaling in macrophage, respectively. Collectively, the present study unveiled the potential cell-cell communication and underlying mechanism involved in cardiac development, which broadened our insights into developmental biology of heart.



中文翻译:

通过人胎儿心脏中的配体-受体对鉴定细胞间相互作用。

心脏是胚胎发生过程中形成的第一个器官,其发育是一个复杂的过程。在这项研究中,我们确定了120种配体-受体对,其中包括在9种细胞类型之一中特异性表达的65个配体和58个受体。细胞比例的相关性分析表明,细胞间的接触在人类胎儿心脏中表现出空间模式。具体而言,在心脏发育过程中,心肌细胞(CMs)的比例可能与左心房和心室中内皮细胞的比例呈负相关。相反,随着妊娠,成纤维细胞样细胞和巨噬细胞共同增加。此外,CM中的配体NPPA(利钠肽A)和内皮细胞(EC)的受体NPR3(利钠肽受体3)在心房CM和心内膜细胞中特异性表达,分别表明心房CM可能通过NPPA-NRP3相互作用与心内膜细胞通讯。此外,通过COL1A1 / COL1A2(胶原I型α1/2链)-CD36和CTGF(结缔组织生长因子)-的配体-受体相互作用,在左和右心房中都观察到了成纤维细胞样细胞与巨噬细胞之间的相互作用。 ITGB2(整联蛋白亚基Beta 2)。功能富集分析表明,配体-受体相互作用可能分别与ECs中cGMP-PKG信号传导通路,成纤维细胞样细胞中的PDGF-β信号传导通路和巨噬细胞中的Toll样受体信号传导的细胞内活化有关。总体而言,本研究揭示了心脏发育中潜在的细胞间通讯和潜在机制,

更新日期:2020-08-29
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