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研究揭示斑马鱼心脏再生过程中激活的成纤维细胞状态的起源和功能
2022-07-24 15:45

德国心血管研究中心Jan Philipp Junker、Daniela Panáková等研究人员合作揭示斑马鱼心脏再生过程中激活的成纤维细胞状态的起源和功能。2022年7月21日,《自然—遗传学》杂志在线发表了这项成果。

基于单细胞转录组学和时空分析,研究人员剖析了斑马鱼心脏再生过程中活化细胞状态的多样性。研究人员观察到受伤后出现了几种具有成纤维细胞特征的短暂细胞状态,并概述了表达胶原蛋白12的成纤维细胞的再生功能。为了了解导致心脏再生的一系列事件,研究人员通过高通量系谱追踪确定了这些细胞状态的起源。研究人员发现,激活的成纤维细胞来自两个不同的来源:心外膜和心内膜。在机制上,研究人员确定Wnt信号是心内膜成纤维细胞反应的调节因子。

总之,这项工作确定了有助于心脏再生的专门的活化成纤维细胞状态,从而开辟了调节脊椎动物心脏再生能力的可能方法。

据介绍,成年斑马鱼的心脏在受伤后有很强的再生能力。然而,再生微环境的组成在很大程度上仍然难以捉摸。

附:英文原文

Title: Origin and function of activated fibroblast states during zebrafish heart regeneration

Author: Hu, Bo, Lelek, Sara, Spanjaard, Bastiaan, El-Sammak, Hadil, Simes, Mariana Guedes, Mintcheva, Janita, Aliee, Hananeh, Schfer, Ronny, Meyer, Alexander M., Theis, Fabian, Stainier, Didier Y. R., Pankov, Daniela, Junker, Jan Philipp

Issue&Volume: 2022-07-21

Abstract: The adult zebrafish heart has a high capacity for regeneration following injury. However, the composition of the regenerative niche has remained largely elusive. Here, we dissected the diversity of activated cell states in the regenerating zebrafish heart based on single-cell transcriptomics and spatiotemporal analysis. We observed the emergence of several transient cell states with fibroblast characteristics following injury, and we outlined the proregenerative function of collagen-12-expressing fibroblasts. To understand the cascade of events leading to heart regeneration, we determined the origin of these cell states by high-throughput lineage tracing. We found that activated fibroblasts were derived from two separate sources: the epicardium and the endocardium. Mechanistically, we determined Wnt signalling as a regulator of the endocardial fibroblast response. In summary, our work identifies specialized activated fibroblast cell states that contribute to heart regeneration, thereby opening up possible approaches to modulating the regenerative capacity of the vertebrate heart. Single-cell RNA sequencing and spatiotemporal analysis of the regenerating zebrafish heart identify transient proregenerative fibroblast-like cells that are derived from the epicardium and the endocardium. Wnt signalling regulates the endocardial fibroblast response.

DOI: 10.1038/s41588-022-01129-5

Source: https://www.nature.com/articles/s41588-022-01129-5

Nature Genetics:《自然—遗传学》,创刊于1992年。隶属于施普林格·自然出版集团,最新IF:41.307
官方网址:https://www.nature.com/ng/
投稿链接:https://mts-ng.nature.com/cgi-bin/main.plex


本期文章:《自然—遗传学》:Online/在线发表

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