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斑马鱼和青鳉的相互分析表明，利用免疫反应可促进心脏再生。

Reciprocal analyses in zebrafish and medaka reveal that harnessing the immune response promotes cardiac regeneration.

作者信息

Lai Shih-Lei, Marín-Juez Rubén, Moura Pedro Luís, Kuenne Carsten, Lai Jason Kuan Han, Tsedeke Ayele Taddese, Guenther Stefan, Looso Mario, Stainier Didier Yr

机构信息

Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.

ECCPS Bioinformatics and Deep Sequencing Platform, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.

出版信息

Elife. 2017 Jun 20;6:e25605. doi: 10.7554/eLife.25605.

DOI:10.7554/eLife.25605
PMID:28632131
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5498136/
Abstract

Zebrafish display a distinct ability to regenerate their heart following injury. However, this ability is not shared by another teleost, the medaka. In order to identify cellular and molecular bases for this difference, we performed comparative transcriptomic analyses following cardiac cryoinjury. This comparison points to major differences in immune cell dynamics between these models. Upon closer examination, we observed delayed and reduced macrophage recruitment in medaka, along with delayed neutrophil clearance. To investigate the role of immune responses in cardiac regeneration, we delayed macrophage recruitment in zebrafish and observed compromised neovascularization, neutrophil clearance, cardiomyocyte proliferation and scar resolution. In contrast, stimulating Toll-like receptor signaling in medaka enhanced immune cell dynamics and promoted neovascularization, neutrophil clearance, cardiomyocyte proliferation and scar resolution. Altogether, these data provide further insight into the complex role of the immune response during regeneration, and serve as a platform to identify and test additional regulators of cardiac repair.

摘要

斑马鱼在心脏受伤后展现出独特的心脏再生能力。然而，另一种硬骨鱼——青鳉却不具备这种能力。为了确定造成这种差异的细胞和分子基础，我们在心脏冷冻损伤后进行了比较转录组分析。这种比较揭示了这些模型在免疫细胞动态方面的主要差异。经过更仔细的观察，我们发现青鳉体内巨噬细胞的募集延迟且数量减少，同时中性粒细胞的清除也延迟。为了研究免疫反应在心脏再生中的作用，我们在斑马鱼中延迟巨噬细胞的募集，结果观察到新生血管形成受损、中性粒细胞清除延迟、心肌细胞增殖受影响以及瘢痕消退延迟。相反，在青鳉中刺激Toll样受体信号增强了免疫细胞动态，并促进了新生血管形成、中性粒细胞清除、心肌细胞增殖以及瘢痕消退。总之，这些数据为再生过程中免疫反应的复杂作用提供了进一步的见解，并为识别和测试心脏修复的其他调节因子提供了一个平台。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bc1/5498136/bba0cdd28ea8/elife-25605-fig9.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bc1/5498136/bba0cdd28ea8/elife-25605-fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bc1/5498136/043cccf60f1c/elife-25605-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bc1/5498136/12407c460578/elife-25605-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bc1/5498136/facacfb82fd5/elife-25605-fig2-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bc1/5498136/05b818c16914/elife-25605-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bc1/5498136/ef3304cc4723/elife-25605-fig3-figsupp1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bc1/5498136/9848244d2eeb/elife-25605-fig4-figsupp2.jpg
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