Hematopoietic stem cell commitment

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展中起着关键作用，其中最重要的是造血干细胞(HSC)承诺的控制。了解这一过程对于理解HSC的功能和自我更新是至关重要的，这种理解将导致对HSC用于治疗目的的操作以及对涉及HSC的疾病过程的新的见解，包括白血病。最后，在理解HSC承诺方面的进展将成为理解其他类型干细胞的模型。这项名为“造血干细胞承诺”的项目由4个项目组成，所有这些项目都是相互关联的，并侧重于了解HSC调节和功能的某些方面。这些项目包括：项目1：“造血干细胞的承诺的分支点”(项目负责人：哈佛医学院Dana Farber癌症研究所的Koichi Akashi；项目2：“造血干细胞的信号转导机制”(项目负责人：麻省大学医学中心伍斯特分校Roger J.Davis)；项目3：“造血干细胞中的RUNX1”(项目负责人：斯克里普斯研究所张栋儿)；项目4：“C/EBPα在造血中的调控”(项目负责人：哈佛医学院贝斯以色列女执事医学中心Daniel G.Tenen)。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。生物统计核心将为统计设计和分析提供指导。 公共卫生相关性：通过结合各种方法，包括转录调控、信号转导以及基因敲除和敲除小鼠的研究，我们将提供关于干细胞功能调控的有价值的新信息。

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.