成年斑马鱼的韧带损伤触发ECM重塑和细胞去分化以实现无瘢痕再生。

IF 6.4 1区 医学 Q1 CELL & TISSUE ENGINEERING npj Regenerative Medicine Pub Date : 2023-09-19 DOI:10.1038/s41536-023-00329-9
Troy Anderson, Julia Mo, Ernesto Gagarin, Desmarie Sherwood, Maria Blumenkrantz, Eric Mao, Gianna Leon, Hailey Levitz, Hung-Jhen Chen, Kuo-Chang Tseng, Peter Fabian, J Gage Crump, Joanna Smeeton
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引用次数: 0

摘要

创伤后,哺乳动物韧带的愈合通常与纤维化瘢痕形成有关,而不是无瘢痕再生。相比之下,我们在这里表明,支撑成年斑马鱼下颌关节的韧带能够快速完全无疤痕愈合。手术切断下颌关节韧带后,我们观察到切口附近的韧带组织断裂,伤口内间充质组织扩张,然后细胞外基质(ECM)重塑为正常的韧带形态。切断后成熟韧带细胞的谱系追踪显示,它们去分化,经历细胞周期重新进入,并有助于再生韧带。再生韧带的单细胞RNA测序揭示了ECM基因在神经嵴衍生的间充质细胞以及表达内肽酶编码基因legumain的多种免疫细胞中的动态表达。对legumain突变斑马鱼的分析表明,需要早期ECM重塑和有效的韧带再生。我们的研究建立了一种新的成人无瘢痕韧带再生模型,并强调了免疫性间充质串扰在启动再生的ECM重塑中的作用。
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Ligament injury in adult zebrafish triggers ECM remodeling and cell dedifferentiation for scar-free regeneration.

After traumatic injury, healing of mammalian ligaments is typically associated with fibrotic scarring as opposed to scar-free regeneration. In contrast, here we show that the ligament supporting the jaw joint of adult zebrafish is capable of rapid and complete scar-free healing. Following surgical transection of the jaw joint ligament, we observe breakdown of ligament tissue adjacent to the cut sites, expansion of mesenchymal tissue within the wound site, and then remodeling of extracellular matrix (ECM) to a normal ligament morphology. Lineage tracing of mature ligamentocytes following transection shows that they dedifferentiate, undergo cell cycle re-entry, and contribute to the regenerated ligament. Single-cell RNA sequencing of the regenerating ligament reveals dynamic expression of ECM genes in neural-crest-derived mesenchymal cells, as well as diverse immune cells expressing the endopeptidase-encoding gene legumain. Analysis of legumain mutant zebrafish shows a requirement for early ECM remodeling and efficient ligament regeneration. Our study establishes a new model of adult scar-free ligament regeneration and highlights roles of immune-mesenchyme cross-talk in ECM remodeling that initiates regeneration.

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来源期刊
npj Regenerative Medicine
npj Regenerative Medicine Engineering-Biomedical Engineering
CiteScore
10.00
自引率
1.40%
发文量
71
审稿时长
12 weeks
期刊介绍: Regenerative Medicine, an innovative online-only journal, aims to advance research in the field of repairing and regenerating damaged tissues and organs within the human body. As a part of the prestigious Nature Partner Journals series and in partnership with ARMI, this high-quality, open access journal serves as a platform for scientists to explore effective therapies that harness the body's natural regenerative capabilities. With a focus on understanding the fundamental mechanisms of tissue damage and regeneration, npj Regenerative Medicine actively encourages studies that bridge the gap between basic research and clinical tissue repair strategies.
期刊最新文献
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