Investigating the heterogeneity and coordination of hematopoietic stem cells

研究造血干细胞的异质性和协调性

• 批准号: 10454787
• 负责人: Rong Lu
• 金额: $ 94.64万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10454787
• 关键词: Address; Age; Aging; Basic Science; Behavior; Blood; Bone Marrow Transplantation; Bone marrow failure; Cells; Diagnosis; Disease; Dysmyelopoietic Syndromes; Foundations; Genes; Hematological Disease; Hematopoietic; Hematopoietic Stem Cell heterogeneity; Hematopoietic stem cells; Heterogeneity; Human; Immune System Diseases; Individual; Injury; Knowledge; Maps; Medicine; Molecular; Molecular Profiling; Mus; Mutation; Myeloproliferative disease; Natural regeneration; Organ; Organism; Pathogenesis; Regulation; Research; Systems Biology; Technology; Therapeutic Uses; Tissues; Transplantation; improved; leukemia; novel; programs; repaired; self-renewal; single cell analysis; stem cell therapy; stem cells

Project Summary: Stem cells replenish tissues and organs over an organism’s lifetime and can repair damage after injury. With their special capacities for self-renewal and differentiation, stem cells promise to revolutionize medicine. To develop better and safer stem cell therapies, it is critically important to improve the understanding of stem cell regulation. Most of the knowledge about stem cell regulation comes from studies that investigate the aggregate behaviors of thousands to millions of stem cells. However, recent studies suggest that individual hematopoietic stem cells (HSCs) behave substantially differently from one another in both mice and humans. These newly discovered inter-cellular differences present exciting new opportunities for studying HSC regulation. However, they also present significant technical challenges that are difficult to address with conventional approaches. The proposed research program will use a novel systems biology approach combined with quantitative single-cell analysis to determine the cellular and molecular mechanisms underlying HSC heterogeneity and coordination, as well as their influences on aging and the pathogenesis of hematopoietic diseases. Many hematopoietic diseases—such as bone marrow failure, myeloproliferative disorders, myelodysplastic syndromes and other age-associated hematopoietic problems—are initiated by rare cells. The proposed research program will map the precise pathogenesis of these diseases and identify disease founder clones and genes using newly developed single cell tracking and molecular profiling technologies. With these technical advances, the proposed research will also produce new fundamental knowledge about blood regeneration, the foundation of bone marrow transplantation. The long-term objective is to apply the knowledge obtained from the proposed basic research to control blood regeneration for therapeutic use, to detect leukemia and other clonal diseases at early stages, and to effectively treat diseases with advanced stem cell therapies.

项目概要： 干细胞在生物体的一生中补充组织和器官，并可以修复受伤后的损伤。 干细胞具有自我更新和分化的特殊能力，有望给医学带来革命性的变化。 为了开发更好、更安全的干细胞疗法，提高对干细胞的理解至关重要 大多数有关干细胞调控的知识来自于研究干细胞调控。 然而，最近的研究表明个体的行为。 小鼠和人类的造血干细胞 (HSC) 的行为显着不同。 这些新发现的细胞间差异为研究 HSC 提供了令人兴奋的新机会 然而，它们也带来了难以解决的重大技术挑战。 拟议的研究计划将使用一种新颖的系统生物学方法。 结合定量单细胞分析以确定潜在的细胞和分子机制 HSC的异质性和协调性及其对衰老和发病机制的影响 许多造血系统疾病，例如骨髓衰竭、骨髓增生性疾病。 疾病、骨髓增生异常综合征和其他与年龄相关的造血问题——由罕见的疾病引起 拟议的研究计划将绘制这些疾病的精确发病机制并进行鉴定。 使用新开发的单细胞追踪和分子谱分析疾病创始人克隆和基因 随着这些技术的进步，拟议的研究也将产生新的基础。 有关血液再生的知识，骨髓移植的基础。 是应用从拟议的基础研究中获得的知识来控制血液再生 治疗用途，早期发现白血病和其他克隆性疾病，并有效治疗疾病 先进的干细胞疗法。