Directing Stem Cells to the Adipocyte Lineage in Infantile Hemangiomas

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Project Summary/Abstract Infantile hemangiomas (IH) are the most common tumors of infancy, with a prevalence of upwards of 25% in premature babies in the United States. IH appear on average between 2 weeks to 4 months after birth, most commonly on the head and neck region. More severe hemangiomas can occur around vital internal organs, leading to complications. These tumors proliferate and expand up to 6-12 months of age, then most slowly involute into fibro-fatty tissue containing adipocytes over the course of 3-5 years. Infantile hemangiomas are not malignant; however, upwards of ~25% require medical treatment as bleeding, ulceration, and interference with vital structures (eyes, mouth, etc.) can occur. The slow progression of the involution stage can also be a psychological burden to parents and children. Our long-term goal is to use our laboratory’s expertise in adipocyte development to identify the adipocyte precursor in these tumors, delineate the transcriptional mechanisms leading to the activation of the adipogenic program, and devise strategies to speed up the natural process by which these tumors convert into fat tissue. The immediate goals of this two-year proposal are to 1) elucidate the cellular landscape of proliferating and involuting infantile hemangiomas using single-cell RNA sequencing and single-cell ATAC sequencing technologies, and 2) characterize the functional properties of IH-derived adipocyte precursors using novel in vitro and in vivo models developed in our laboratory. The development of novel therapeutic strategies is needed in order to ease the physical and psychological stress on these children and their families, eliminate the need for alternative medical therapies, and decrease the need for costly and invasive surgical procedures to remove the tumors.