An organ-wide spatiotemporal transcriptomic and cellular atlas of the regenerating zebrafish heart

Abstract 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-se...

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Main Authors: Lei Li, Meina Lu, Lidong Guo, Xuejiao Zhang, Qun Liu, Meiling Zhang, Junying Gao, Mengyang Xu, Yijian Lu, Fang Zhang, Yao Li, Ruihua Zhang, Xiawei Liu, Shanshan Pan, Xianghui Zhang, Zhen Li, Yadong Chen, Xiaoshan Su, Nannan Zhang, Wenjie Guo, Tao Yang, Jing Chen, Yating Qin, Zhe Zhang, Wei Cui, Lindong Yu, Ying Gu, Huanming Yang, Xun Xu, Jianxun Wang, Caroline E. Burns, C. Geoffrey Burns, Kai Han, Long Zhao, Guangyi Fan, Ying Su
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-59070-0
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Summary:Abstract 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.
ISSN:2041-1723