PUBLICATION
Cloche/Npas4l is a pro-regenerative platelet factor during zebrafish heart regeneration
- Authors
- Hou, J., Song, Y., Xiao, C., Sun, Y., Shen, J., Ma, X., Zhou, Q., Chiu, S.C., Xu, Y., Huang, Y., Chen, Y.G., Zhu, X., Wang, J., Xiong, J.W.
- ID
- ZDB-PUB-250703-8
- Date
- 2025
- Source
- Developmental Cell : (Journal)
- Registered Authors
- Xiong, Jing-Wei
- Keywords
- cloche, heart regeneration, npas4l, platelets, zebrafish
- Datasets
- GEO:GSE224125
- MeSH Terms
-
- Myocytes, Cardiac/cytology
- Myocytes, Cardiac/metabolism
- Blood Platelets*/metabolism
- Endothelial Cells/cytology
- Endothelial Cells/metabolism
- Animals
- Regeneration*/physiology
- Zebrafish*/genetics
- Zebrafish*/metabolism
- Signal Transduction
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- Cell Proliferation
- Heart*/physiology
- Basic Helix-Loop-Helix Transcription Factors*/genetics
- Basic Helix-Loop-Helix Transcription Factors*/metabolism
- PubMed
- 40602409 Full text @ Dev. Cell
Citation
Hou, J., Song, Y., Xiao, C., Sun, Y., Shen, J., Ma, X., Zhou, Q., Chiu, S.C., Xu, Y., Huang, Y., Chen, Y.G., Zhu, X., Wang, J., Xiong, J.W. (2025) Cloche/Npas4l is a pro-regenerative platelet factor during zebrafish heart regeneration. Developmental Cell. :.
Abstract
Zebrafish has full capacity of heart regeneration, but little is known about how blood cells, especially platelets, are involved in this regenerative process. Here, we report that cloche/npas4l is a pro-regenerative platelet factor for heart regeneration. We found that haploinsufficiency of npas4l disrupted cardiomyocyte (CM) and endothelial cell (EC) proliferation and heart regeneration after injury. A single-cell transcriptomic atlas identified that npas4l was dynamically expressed in platelets after heart injury and controlled robust interactions between platelet-CMs or -ECs. Decreasing platelets impaired CM/EC proliferation, and overexpression of npas4l in platelets sufficiently induced CM/EC proliferation in uninjured hearts, as well as rescued CM/EC proliferation defects in cloche mutants. Mechanistically, Npas4l positively controlled a panel of ligand expression, including bmp6 in platelets, to fine-tune CM proliferation and heart regeneration. Therefore, this work demonstrates platelet Npas4l signaling and presents mechanisms on how platelets modulate CM/EC proliferation via ligand-receptor network during zebrafish heart regeneration.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping