PUBLICATION
ptx3a+ fibroblast/epicardial cells provide a transient macrophage niche to promote heart regeneration
- Authors
- Sun, J., Peterson, E.A., Chen, X., Wang, J.
- ID
- ZDB-PUB-240413-1
- Date
- 2024
- Source
- Cell Reports 43: 114092114092 (Journal)
- Registered Authors
- Wang, Jinhu
- Keywords
- CP: Immunology, CP: Stem cell research, csf1a, epicardium, heart, macrophage, ptx3a, regeneration, zebrafish
- MeSH Terms
-
- Animals
- C-Reactive Protein/genetics
- C-Reactive Protein/metabolism
- Fibroblasts*/metabolism
- Heart*/physiology
- Heart Injuries/metabolism
- Heart Injuries/pathology
- Macrophages*/metabolism
- Pericardium/cytology
- Pericardium/metabolism
- Regeneration*/physiology
- Serum Amyloid P-Component/genetics
- Serum Amyloid P-Component/metabolism
- Zebrafish*/metabolism
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 38607913 Full text @ Cell Rep.
Citation
Sun, J., Peterson, E.A., Chen, X., Wang, J. (2024) ptx3a+ fibroblast/epicardial cells provide a transient macrophage niche to promote heart regeneration. Cell Reports. 43:114092114092.
Abstract
Macrophages conduct critical roles in heart repair, but the niche required to nurture and anchor them is poorly studied. Here, we investigated the macrophage niche in the regenerating heart. We analyzed cell-cell interactions through published single-cell RNA sequencing datasets and identified a strong interaction between fibroblast/epicardial (Fb/Epi) cells and macrophages. We further visualized the association of macrophages with Fb/Epi cells and the blockage of macrophage response without Fb/Epi cells in the regenerating zebrafish heart. Moreover, we found that ptx3a+ epicardial cells associate with reparative macrophages, and their depletion resulted in fewer reparative macrophages. Further, we identified csf1a expression in ptx3a+ cells and determined that pharmacological inhibition of the csf1a pathway or csf1a knockout blocked the reparative macrophage response. Moreover, we found that genetic overexpression of csf1a enhanced the reparative macrophage response with or without heart injury. Altogether, our studies illuminate a cardiac Fb/Epi niche, which mediates a beneficial macrophage response after heart injury.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping