GLI1⁺ perivascular cells in angiogenesis and vascular remodeling: mechanisms and disease relevance

Abstract

Glioma-associated oncogene family zinc finger 1 (GLI1) encodes a major transcriptional effector of Hedgehog (HH) signaling. In adult tissues, GLI1 expression also marks perivascular mesenchymal populations with progenitor-like and injury-responsive properties. Over the past decade, lineage-tracing and single-cell studies in mice have shown that GLI1⁺ cells are not static: they may support vessel stability and repair, but they can also be recruited into maladaptive remodeling programs. For angiogenesis research, the key question is therefore not simply whether GLI1⁺ cells are present, but which state they adopt and what pushes them toward regeneration, fibrosis, neomuscularization, or tumor-supportive vasculature. Here, we synthesize how GLI1⁺ cells and GLI1 pathway activity intersect with endothelial, immune, mural-cell, and extracellular matrix (ECM) programs across physiological angiogenesis and major disease settings, including tumor angiogenesis, pulmonary vascular remodeling, and fibrotic vasculopathy. We also indicate where direct lineage-based evidence is available, where the evidence is still inferential, and which cell-state-specific nodes appear most realistic for therapeutic targeting.