Directing Stem Cells to the Adipocyte Lineage in Infantile Hemangiomas

项目总结/摘要 婴儿血管瘤（IH）是婴儿期最常见的肿瘤， 在美国，早产儿中有25%。IH平均出现在出生后2周至4个月， 最常见于头部和颈部区域。更严重的血管瘤可能发生在重要的内脏器官周围， 导致并发症。这些肿瘤在6-12个月大时增殖和扩大，然后最慢 在3-5年的过程中逐渐发展成含有脂肪细胞的纤维脂肪组织。婴儿血管瘤不是 恶性;然而，约25%以上需要药物治疗，如出血，溃疡和干扰 重要结构（眼睛、嘴巴等）可能发生。退化阶段的缓慢进展也可能是一种 给父母和孩子带来心理负担。 我们的长期目标是利用我们实验室在脂肪细胞发育方面的专业知识， 这些肿瘤中的前体，描绘了导致脂肪形成的激活的转录机制。 程序，并制定策略，以加快这些肿瘤转化为脂肪组织的自然过程。 这项为期两年的提案的近期目标是：1）阐明细胞增殖的细胞景观， 使用单细胞RNA测序和单细胞ATAC测序的消退婴儿血管瘤 技术，和2）使用新的体外实验表征IH衍生的脂肪细胞前体的功能特性， 和我们实验室开发的体内模型。需要开发新的治疗策略， 为了减轻这些儿童及其家庭的身心压力， 替代医学疗法，并减少对昂贵和侵入性手术程序的需要，以去除 肿瘤的

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.