Single-cell RNA Sequencing Discovered Subtypes Associated with Angiogenesis and Propranolol Treatment in Infantile Hemangioma

Infantile hemangioma (IH), a benign vascular tumor of infancy, is characterized by rapid postnatal growth and subsequent spontaneous resolution. Although propranolol, initially developed for cardiovascular disorders, is the primary treatment for IH, its precise molecular mechanisms remain incompletely elucidated. This study employed single-cell RNA sequencing (scRNA-seq) to generate a comprehensive cellular atlas comprising eight tissues from three IH infants, sampled both before and after propranolol treatment, alongside two normal infant skin samples, yielding 103,082 cells. Concurrently, tumor-normal tissue paired whole-genome sequencing (WGS) was conducted on samples from 13 IH infants. To provide a comprehensive genomic landscape, we also characterized germline and somatic variations. scRNA-seq analysis identified two distinct propranolol-targeted IH-specific cell subtypes: APLN + hemangioma endothelial cells (HemECs), associated with angiogenesis, and CENPF + hemangioma pericytes (Hem-Pericytes), associated with IH proliferation. WGS revealed that the majority of mutations resided in intronic regions, somatic copy number alterations changed weakly, and that most somatic mutations were clonal. Functional validation demonstrated that propranolol treatment suppressed APLN transcription. Overall, this integrative study delineated two distinct IH-specific cell subtypes, with detailed characterization of germline/somatic mutations, copy number variations, and clonal evolution in IH.