Single-Cell RNA Sequencing Reveals Bidirectional Development of Infantile Hemangioma

Infantile hemangioma (IH) affects 5-10% of all infants and up to 30% of premature newborns. Further understanding of disease mechanisms and therapeutic strategies requires a deeper knowledge of IH in humans. In this study, we performed single-cell RNA sequencing on hemangioma samples from 3 infants diagnosed with IH. A total of 36,237 high-quality cells were clustered into 10 major cell types, including endothelial cells and hemangioma mural cells. Endothelial cells in IH exhibit strong proliferative capacity and heterogeneity. Furthermore, cell-cell communication analysis and immunofluorescence colocalization revealed that hemangioma mural cells, which constitute >50% of IH, can release ligands such as VEGFA and PGF and act on endothelial cells, thus promoting endothelial cell proliferation and angiogenesis. We also found that the expression levels of VEGFA and Ki-67 are significantly higher in IH than in normal infant skin tissue. Finally, we also found that adrenaline receptor beta 1 is specifically expressed in EC1 and EC2, adrenaline receptor beta 2 is specifically expressed in EC3, and adrenoceptor alpha is specifically expressed in hemangioma mural cells. In summary, our study provides a cellular atlas of proliferative-phase IH and reveals the important roles of endothelial cells and hemangioma mural cells in the development of IH.