Key cellular subpopulations and mechanisms of propranolol in infantile hemangioma: insights from single-cell omics

Infantile hemangioma (IH) is the most common benign vascular tumor in infancy, characterized by rapid proliferation followed by spontaneous involution. Despite propranolol being established as first-line therapy, the cellular basis of this biphasic behavior and the mechanisms underlying propranolol efficacy have remained incompletely understood. Single-cell RNA sequencing (scRNA-seq) has recently enabled high-resolution dissection of IH tissue composition, revealing a previously uncharacterized cellular heterogeneity that advances our understanding of both disease pathogenesis and drug action. Here we systematically review these advances. Within the vascular compartment, APLN-positive endothelial cells with tip cell characteristics and CENPF-positive proliferative pericytes are identified as IH-specific subpopulations enriched in the proliferating phase and suppressed by propranolol treatment. CD146-positive mural cells, which constitute the predominant cell population in IH, exhibit a dynamic proangiogenic-to-adipogenic transition that may underlie the spontaneous proliferation-to-involution switch. Beyond vascular cells, macrophages, mast cells, and telocytes within the stromal microenvironment contribute to lesion progression and modulate drug response. These findings support a model in which IH progression is governed by dynamic shifts in dominant cellular subpopulations rather than endothelial hyperproliferation alone, and suggest how propranolol may act across multiple cell types. These insights may inform efforts to predict treatment response, assess rebound risk, and refine therapeutic strategies for IH.