Cell Fate Regulation During the Development of Infantile Hemangioma

As the most common benign vascular tumor in infants, infantile hemangioma (IH) is characterized by rapid growth and vasculogenesis early in infancy, followed by spontaneous involution into fibrofatty tissues over time. Extensive evidence suggests that IH originates from hemangioma stem cells (HemSCs), a group of stem cells with clonal expansion and multi-directional differentiation capacity. However, the intricate mechanisms governing the cell fate transition of HemSCs during IH development remain elusive. Here we comprehensively examine the cellular composition of IH, emphasizing the nuanced properties of various IH cell types and their correlation with the clinical features of the tumor. We also summarize the current understanding of the regulatory pathways directing HemSC differentiation into endothelial cells (ECs), pericytes, and adipocytes throughout the stages of IH progression and involution. Furthermore, we discuss recent advances in unraveling the transcriptional and epigenetic regulation of EC and adipocyte development under physiological conditions, which offer crucial perspectives for understanding IH pathogenesis.