Hematopoietic stem cell commitment

造血干细胞定向

• 批准号: 8142133
• 负责人: DANIEL G TENEN
• 金额: $ 142.39万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8142133
• 关键词: Biostatistics Core; CCAAT-Enhancer-Binding Proteins; Cell physiology; Communication; Complex; Dana-Farber Cancer Institute; Development; Disease; Hematopoiesis; Hematopoietic; Hematopoietic stem cells; Israel; Knock-out; Lead; Massachusetts; Medical center; Modeling; Mus; Play; Process; Regulation; Research Institute; Role; Signal Transduction; Stem cells; Therapeutic; Transcriptional Regulation; Universities; design; insight; leukemia; medical schools; meetings; novel; programs; public health relevance; self-renewal

DESCRIPTION, OVERALL (provided by applicant): A complex interaction of different processes play a critical role in the development of hematopoietic lineages, and among the most important are the controls of hematopoietic stem cell (HSC) commitment. Understanding this process is critical to understanding HSC function as well as self-renewal, and this understanding will lead to novel insights into manipulation of HSC for therapeutic purposes, as well as understanding disease processes which involve HSC, including leukemia. Finally, advances in understanding HSC commitment will serve as a model for understanding other types of stem cells. This program, "Hematopoietic Stem Cell Commitment," consists of 4 projects, all of which are interrelated and focused on understanding some aspect of HSC regulation and function. They include: Project 1: "Branching points of hematopoietic stem cell commitment", (Project Leader: Koichi Akashi, Dana Farber Cancer Institute, Harvard Medical School; Project 2, "Signal Transduction Mechanisms in Hematopoietic Stem Cells" (Project Leader: Roger J. Davis, University of Massachusetts Medical Center, Worcester); Project 3: "Runx1 in hematopoietic stem cells" (Project Leader: Dong-Er Zhang, Scripps Research Institute); and Project 4, "Regulation of C/EBP alpha in hematopoiesis" (Project Leader: Daniel G. Tenen, Beth Israel Deaconess Medical Center, Harvard Medical School). The administrative core will be responsible for many interactive functions of the program, including regular meetings, seminars, and communication among projects. A Biostatistics Core will provide direction with statistical design and analysis. PUBLIC HEALTH RELEVANCE: By combining a variety of approaches, including studies of transcriptional regulation, signal transduction, and knockout and knockin mice, we will provide valuable new information concerning the regulation of stem cell function.

总体描述（由申请人提供）：不同过程的复杂相互作用在造血谱系的发育中起关键作用，其中最重要的是造血干细胞（HSC）定型的控制。理解这一过程对于理解HSC功能以及自我更新至关重要，并且这种理解将导致对HSC用于治疗目的的操纵的新见解，以及理解涉及HSC的疾病过程，包括白血病。最后，在理解HSC承诺方面的进展将作为理解其他类型干细胞的模型。这个项目，“造血干细胞承诺”，包括4个项目，所有这些都是相互关联的，并侧重于了解HSC的调控和功能的某些方面。它们包括：项目一：“造血干细胞定型的分支点”，（项目负责人：Koichi Akashi，Dana Farber癌症研究所，哈佛医学院;项目2，“造血干细胞中的信号转导机制”（项目负责人：Roger J. Davis，马萨诸塞州医学中心，伍斯特）;项目3：“造血干细胞中的Runx 1”）（项目负责人：Dong-Er Zhang，Scripps Research Institute）;和项目4，“造血中C/EBP α的调节”（项目负责人：丹尼尔G. Tenen，Beth Israel Deaconess Medical Center，哈佛医学院）。行政核心将负责该计划的许多互动功能，包括定期会议，研讨会和项目之间的沟通。生物统计学核心将提供统计设计和分析的方向。 公共卫生相关性：通过结合多种方法，包括转录调节、信号传导以及敲除和敲入小鼠的研究，我们将提供有关干细胞功能调节的有价值的新信息。