Li Lei, Lu Meina, Guo Lidong, Zhang Xuejiao, Liu Qun, Zhang Meiling, Gao Junying, Xu Mengyang, Lu Yijian, Zhang Fang, Li Yao, Zhang Ruihua, Liu Xiawei, Pan Shanshan, Zhang Xianghui, Li Zhen, Chen Yadong, Su Xiaoshan, Zhang Nannan, Guo Wenjie, Yang Tao, Chen Jing, Qin Yating, Zhang Zhe, Cui Wei, Yu Lindong, Gu Ying, Yang Huanming, Xu Xun, Wang Jianxun, Burns Caroline E, Burns C Geoffrey, Han Kai, Zhao Long, Fan Guangyi, Su Ying
Qingdao Key Laboratory of Marine Genomics, BGI Research, Qingdao, 266555, China.
State Key Laboratory of Genome and Multi-omics Technologies, BGI Research, Shenzhen, 518083, China.
Nat Commun. 2025 Apr 19;16(1):3716. doi: 10.1038/s41467-025-59070-0.
Adult zebrafish robustly regenerate injured hearts through a complex orchestration of molecular and cellular activities. However, this remarkable process, which is largely non-existent in humans, remains incompletely understood. Here, we utilize integrated spatial transcriptomics (Stereo-seq) and single-cell RNA-sequencing (scRNA-seq) to generate a spatially-resolved molecular and cellular atlas of regenerating zebrafish heart across eight stages. We characterize the cascade of cardiomyocyte cell states responsible for producing regenerated myocardium and explore a potential role for tpm4a in cardiomyocyte re-differentiation. Moreover, we uncover the activation of ifrd1 and atp6ap2 genes as a unique feature of regenerative hearts. Lastly, we reconstruct a 4D "virtual regenerating heart" comprising 569,896 cells/spots derived from 36 scRNA-seq libraries and 224 Stereo-seq slices. Our comprehensive atlas serves as a valuable resource to the cardiovascular and regeneration scientific communities and their ongoing efforts to understand the molecular and cellular mechanisms underlying vertebrate heart regeneration.
成年斑马鱼通过分子和细胞活动的复杂协调，强有力地再生受损心脏。然而，这一在人类中基本不存在的显著过程，仍未被完全理解。在这里，我们利用整合空间转录组学（Stereo-seq）和单细胞RNA测序（scRNA-seq），生成了斑马鱼心脏在八个阶段再生过程中的空间分辨分子和细胞图谱。我们描述了负责产生再生心肌的心肌细胞状态级联，并探讨了tpm4a在心肌细胞重新分化中的潜在作用。此外，我们发现ifrd1和atp6ap2基因的激活是再生心脏的一个独特特征。最后，我们重建了一个4D“虚拟再生心脏”，它由来自36个scRNA-seq文库和224个Stereo-seq切片的569,896个细胞/斑点组成。我们的综合图谱为心血管和再生科学界以及他们正在进行的理解脊椎动物心脏再生潜在分子和细胞机制的努力提供了宝贵资源。
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