Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Bad Nauheim, 61231, Germany.
Max Delbrück Center for Molecular Medicine, Robert-Rössle-Straße 10, 13092 Berlin, Germany; DZHK (German Center for Cardiovascular Research), Partner Site Berlin, Berlin, Germany.
Nat Commun. 2017 Nov 15;8(1):1525. doi: 10.1038/s41467-017-01555-8.
Cells can sacrifice their individuality by fusing, but the prevalence and significance of this process are poorly understood. To approach these questions, here we generate transgenic reporter lines in zebrafish to label and specifically ablate fused cells. In addition to skeletal muscle cells, the reporters label cardiomyocytes starting at an early developmental stage. Genetic mosaics generated by cell transplantation show cardiomyocytes expressing both donor- and host-derived transgenes, confirming the occurrence of fusion in larval hearts. These fusion events are transient and do not generate multinucleated cardiomyocytes. Functionally, cardiomyocyte fusion correlates with their mitotic activity during development as well as during regeneration in adult animals. By analyzing the cell fusion-compromised jam3b mutants, we propose a role for membrane fusion in cardiomyocyte proliferation and cardiac function. Together, our findings uncover the previously unrecognized process of transient cardiomyocyte fusion and identify its potential role in cardiac development and function.
细胞可以通过融合来牺牲个体性，但这种过程的普遍性和意义还了解甚少。为了研究这些问题，我们在斑马鱼中生成了转基因报告基因系，以标记和特异性地去除融合细胞。除了骨骼肌细胞，报告基因还在早期发育阶段标记心肌细胞。通过细胞移植产生的遗传嵌合体显示，表达供体和宿主来源转基因的心肌细胞，证实了幼虫心脏中融合的发生。这些融合事件是短暂的，不会产生多核心肌细胞。功能上，心肌细胞融合与它们在发育过程中的有丝分裂活性以及成年动物再生过程中的有丝分裂活性相关。通过分析细胞融合缺陷的 jam3b 突变体，我们提出了膜融合在心肌细胞增殖和心脏功能中的作用。总之，我们的发现揭示了以前未被认识到的短暂心肌细胞融合过程，并确定了其在心脏发育和功能中的潜在作用。
