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：
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
项目类别：
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

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

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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.

项目摘要/摘要婴儿血管瘤（IH）是婴儿期最常见的肿瘤，患病率是以上美国的早产婴儿有25％。 IH平均在出生后2周到4个月之间出现最常见的是头部和颈部区域。可能发生更严重的血管瘤，周围发生重要的内脏器官，导致并发症。这些肿瘤扩散并膨胀到6-12个月大，然后最缓慢在3 - 5年的时间内进入含有脂肪细胞的纤维脂肪组织。婴儿血管瘤不是恶性；但是，高达约25％的人需要医疗作为出血，溃疡和干扰可能发生重要的结构（眼睛，嘴等）。涉嫌阶段的缓慢进展也可能是对父母和孩子的心理烧伤。我们的长期目标是利用实验室在脂肪细胞开发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生物激活的转录机制程序，并制定策略来加快这些肿瘤转化为脂肪组织的自然过程。该为期两年的提案的直接目标是1）阐明了增殖和使用单细胞RNA测序和单细胞ATAC测序参与婴儿血管瘤技术和2）表征使用新型体外体外的IH衍生脂肪细胞前体的功能特性并在我们的实验室开发了体内模型。需要开发新的治疗策略为了减轻对这些孩子及其家人的身体和心理压力，消除了需求替代医疗疗法，并减少了对去除昂贵和侵入性手术程序的需求肿瘤。