Directing Stem Cells to the Adipocyte Lineage in Infantile Hemangiomas

将干细胞引导至婴儿血管瘤的脂肪细胞谱系

• 批准号: 10662659
• 负责人: Rana K Gupta
• 金额: $ 19.97万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10662659
• 关键词: ATAC-seq; Adipocytes; Adipose tissue; Adrenal Cortex Hormones; Adrenergic beta-Antagonists; Age-Months; Agitation; Animal Disease Models; Animal Model; Automobile Driving; Biology; Birth; Blood Vessels; Blood capillaries; Bronchial Hyperreactivity; Caring; Cell Differentiation process; Cell model; Cells; Child; Child Health; Collagen; Common Neoplasm; Computer Analysis; Constipation; Dangerousness; Data; Development; Differentiation Therapy; Disease Progression; Endothelial Cells; Excision; Exhibits; Eye; FDA approved; Family; Fatty acid glycerol esters; Genetic Transcription; Genital; Genitalia; Goals; Growth; Head and neck structure; Hemangioma; Hemorrhage; Human Biology; Hypoglycemia; Hypotension; Hypothyroidism; Immunodeficient Mouse; In Vitro; Incidence; Infant; Iodide Peroxidase; Knowledge; Laboratories; Lead; Life; Lipids; Liver; Low Birth Weight Infant; Low-Level Laser Therapy; Medical; Medical center; Modeling; Molecular; Neoplasms in Vascular Tissue; Nervous System Trauma; Operative Surgical Procedures; Oral; Oral cavity; Organ; Parents; Pharmaceutical Preparations; Premature Infant; Prevalence; Process; Proliferating; Property; Propranolol; Psychological Impact; Psychological Stress; Research; Research Personnel; SLC2A1 gene; Seizures; Signal Transduction; Skin Neoplasms; Sleep; Speed; Strawberry nevus; Structure; Study models; System; Technology; Testing; Texas; Tissues; Transplantation; Tumor Debulking; Tumor stage; Ulcer; United States; XCL1 gene; adipocyte biology; adipocyte differentiation; cell type; clinical predictors; cost; endothelial stem cell; experimental study; human tissue; in vivo; in vivo Model; infancy; innovation; insight; novel; novel therapeutic intervention; pre-clinical; premature; programs; psychologic; rosiglitazone; side effect; single-cell RNA sequencing; stem cell proliferation; stem cells; transplant model; treatment strategy; tumor; tumor growth; tumor progression

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.

项目概要/摘要 婴儿血管瘤（IH）是婴儿期最常见的肿瘤，患病率高达 在美国，早产儿的比例为 25%。 IH 平均出现在出生后 2 周至 4 个月之间， 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 年内逐渐退化为含有脂肪细胞的纤维脂肪组织。婴儿血管瘤不是 恶性；然而，超过 25% 的人需要治疗，因为出血、溃疡和干扰 重要结构（眼睛、嘴巴等）可能会发生。退化阶段的缓慢进展也可以是 给家长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来识别脂肪细胞 这些肿瘤的前体，描绘了导致脂肪形成激活的转录机制 计划，并制定策略来加速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) 阐明增殖和增殖的细胞景观 使用单细胞 RNA 测序和单细胞 ATAC 测序使婴儿血管瘤消退 技术，2) 使用新型体外技术表征 IH 衍生的脂肪细胞前体的功能特性 以及我们实验室开发的体内模型。需要开发新的治疗策略 为了缓解这些儿童及其家人的身心压力，消除对 替代医学疗法，并减少昂贵的侵入性手术切除的需要 肿瘤。