Zebrafish scxa+ Perivascular Cells Limit Coronary Vessel Expansion via Collagen-Derived Signals

Researchers at Weill Cornell Medicine used single-cell transcriptomics and lineage tracing in injured zebrafish hearts to show that hypoxia-activated epicardial progenitors differentiate into scxa-expressing cells that wrap coronary vessels and produce a collagen-derived peptide inhibiting excessive angiogenesis. Absolute vessel density increased 1.8-fold when scxa was knocked down, while overexpression reduced branching by 35 percent compared with controls. The work extends prior findings that epicardial signals coordinate myocardial and vascular regrowth, revealing a negative-feedback loop absent from earlier bulk RNA-seq studies of the same model. The discovery connects to mammalian data showing SCX upregulation in post-infarct fibroblasts that drive fibrosis rather than regeneration. Human epicardial organoid experiments will be required to test whether the same perivascular program can be redirected away from scar formation. Current evidence remains limited to zebrafish genetics; no functional SCX data yet exist in human cardiac progenitors. Next steps include testing whether transient SCX agonism in human iPSC-derived epicardial cells can promote vessel stabilization without fibrosis in cardiac organoids, with results expected within 24 months.