Heterogeneous pdgfrb+ cells regulate coronary vessel development and revascularization during heart regeneration

Area of Science:

• Cardiovascular Biology
• Developmental Biology
• Regenerative Medicine

Background:

• Coronary blood vessels in zebrafish hearts originate from endothelial cells in the atrioventricular canal.
• The role of specific cell populations, like those expressing pdgfrb, in coronary development and heart regeneration is not fully understood.

Purpose of the Study:

• To investigate the function of pdgfrb-expressing cells in coronary vessel development and heart regeneration in zebrafish.
• To identify the specific cell types and molecular mechanisms involved.

Main Methods:

• Utilized zebrafish models with pdgfrb mutations.
• Employed single-cell RNA sequencing to identify cell populations.
• Analyzed gene expression patterns in wild-type and mutant zebrafish during heart development and regeneration.

Main Results:

• pdgfrb is expressed in epicardium-derived cells (EPDCs) and mural cells, which are critical for coronary vessel formation.
• pdgfrb mutant fish exhibit significant defects in mural cell recruitment and coronary development.
• pdgfrb+ EPDCs and mural cells play a dynamic role in heart regeneration, with specific genes like mdka being upregulated.
• While pdgfrb mutants show regeneration defects, mdka mutants do not, highlighting pdgfrb's essential role.

Conclusions:

• Heterogeneous pdgfrb+ cells, encompassing EPDCs and mural cells, are indispensable for both the development of coronary vasculature and the regenerative capacity of the zebrafish heart.
• pdgfrb signaling is a key regulator in the processes of coronary angiogenesis and cardiac repair.