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

基本信息

批准号：
10311391
负责人：
Rana K Gupta
金额：
$ 24.59万
依托单位：
UT SOUTHWESTERN MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-08-01 至 2022-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10311391
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

项目摘要

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，25% 的早产儿平均在出生后 2 周至 4 个月内出现。最常见于头部和颈部区域，重要内脏器官周围可能出现更严重的血管瘤，这些肿瘤在 6-12 个月大时会增殖并扩大，然后增殖速度最慢。婴儿血管瘤不会在 3-5 年内逐渐退化为含有脂肪细胞的纤维脂肪组织。恶性；然而，超过 25% 需要治疗，如出血、溃疡和干扰重要结构（眼睛、嘴等）也可能发生退化阶段的缓慢进展。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。这个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。