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

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

doi:10.1038/s41467-025-59070-0

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

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

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

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.

Original language	English
Article number	3716
Journal	Nature Communications
Volume	16
Issue number	1
DOIs	https://doi.org/10.1038/s41467-025-59070-0
State	Published - Dec 2025
Externally published	Yes

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Li, L., Lu, M., Guo, L., Zhang, X., Liu, Q., Zhang, M., Gao, J., Xu, M., Lu, Y., Zhang, F., Li, Y., Zhang, R., Liu, X., Pan, S., Zhang, X., Li, Z., Chen, Y., Su, X., Zhang, N., ... Su, Y. (2025). An organ-wide spatiotemporal transcriptomic and cellular atlas of the regenerating zebrafish heart. Nature Communications, 16(1), Article 3716. https://doi.org/10.1038/s41467-025-59070-0

@article{9086afcf3bda4f9fb804167ecc8781c0,

title = "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-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.",

author = "Lei Li and Meina Lu and Lidong Guo and Xuejiao Zhang and Qun Liu and Meiling Zhang and Junying Gao and Mengyang Xu and Yijian Lu and Fang Zhang and Yao Li and Ruihua Zhang and Xiawei Liu and Shanshan Pan and Xianghui Zhang and Zhen Li and Yadong Chen and Xiaoshan Su and Nannan Zhang and Wenjie Guo and Tao Yang and Jing Chen and Yating Qin and Zhe Zhang and Wei Cui and Lindong Yu and Ying Gu and Huanming Yang and Xun Xu and Jianxun Wang and Burns, \{Caroline E.\} and Burns, \{C. Geoffrey\} and Kai Han and Long Zhao and Guangyi Fan and Ying Su",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2025.",

year = "2025",

month = dec,

doi = "10.1038/s41467-025-59070-0",

language = "英语",

volume = "16",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

number = "1",

}

Li, L, Lu, M, Guo, L, Zhang, X, Liu, Q, Zhang, M, Gao, J, Xu, M, Lu, Y, Zhang, F, Li, Y, Zhang, R, Liu, X, Pan, S, Zhang, X, Li, Z, Chen, Y, Su, X, Zhang, N, Guo, W, Yang, T, Chen, J, Qin, Y, Zhang, Z, Cui, W, Yu, L, Gu, Y, Yang, H, Xu, X, Wang, J, Burns, CE, Burns, CG, Han, K, Zhao, L, Fan, G & Su, Y 2025, 'An organ-wide spatiotemporal transcriptomic and cellular atlas of the regenerating zebrafish heart', Nature Communications, vol. 16, no. 1, 3716. https://doi.org/10.1038/s41467-025-59070-0

TY - JOUR

T1 - An organ-wide spatiotemporal transcriptomic and cellular atlas of the regenerating zebrafish heart

AU - Li, Lei

AU - Lu, Meina

AU - Guo, Lidong

AU - Zhang, Xuejiao

AU - Liu, Qun

AU - Zhang, Meiling

AU - Gao, Junying

AU - Xu, Mengyang

AU - Lu, Yijian

AU - Zhang, Fang

AU - Li, Yao

AU - Zhang, Ruihua

AU - Liu, Xiawei

AU - Pan, Shanshan

AU - Zhang, Xianghui

AU - Li, Zhen

AU - Chen, Yadong

AU - Su, Xiaoshan

AU - Zhang, Nannan

AU - Guo, Wenjie

AU - Yang, Tao

AU - Chen, Jing

AU - Qin, Yating

AU - Zhang, Zhe

AU - Cui, Wei

AU - Yu, Lindong

AU - Gu, Ying

AU - Yang, Huanming

AU - Xu, Xun

AU - Wang, Jianxun

AU - Burns, Caroline E.

AU - Burns, C. Geoffrey

AU - Han, Kai

AU - Zhao, Long

AU - Fan, Guangyi

AU - Su, Ying

PY - 2025/12

Y1 - 2025/12

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/105003263572

U2 - 10.1038/s41467-025-59070-0

DO - 10.1038/s41467-025-59070-0

M3 - 文章

C2 - 40253397

AN - SCOPUS:105003263572

SN - 2041-1723

VL - 16

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 3716

ER -

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

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