PUBLICATION

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

Authors
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, C.E., Burns, C.G., Han, K., Zhao, L., Fan, G., Su, Y.
ID
ZDB-PUB-250420-11
Date
2025
Source
Nature communications   16: 37163716 (Journal)
Registered Authors
Burns (Erter), Caroline, Gao, Junying, LU, Meina, Su, Ying, Zhang, Meiling, Zhang, Xuejiao, Zhao, Long
Keywords
none
MeSH Terms
  • Zebrafish*/genetics
  • Zebrafish*/physiology
  • Myocytes, Cardiac/cytology
  • Myocytes, Cardiac/metabolism
  • Single-Cell Analysis
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
  • Transcriptome*/genetics
  • Animals
  • Cell Differentiation/genetics
  • Regeneration*/genetics
  • Regeneration*/physiology
  • Gene Expression Profiling
  • Heart*/physiology
  • Myocardium/cytology
  • Myocardium/metabolism
PubMed
40253397 Full text @ Nat. Commun.
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.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping