Hematopoietic stem cell commitment

概述（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，其中最重要的是对造血干细胞（HSC）承诺的控制。理解这一过程对于理解造血干细胞的功能和自我更新至关重要，这一理解将导致对用于治疗目的的造血干细胞操作的新见解，以及对包括白血病在内的涉及造血干细胞的疾病过程的理解。最后，对HSC承诺的理解将作为理解其他类型干细胞的模型。该项目名为“造血干细胞承诺”（Hematopoietic Stem Cell Commitment），由4个项目组成，所有项目都是相互关联的，重点是了解HSC调控和功能的某些方面。他们包括：项目1：“造血干细胞承诺的分支点”（项目负责人：Koichi Akashi，哈佛医学院Dana Farber癌症研究所），项目2，“造血干细胞的信号转导机制”（项目负责人：Roger J. Davis，马萨诸塞大学伍斯特医学中心）；项目3：“Runx1在造血干细胞中的作用”（项目负责人：张东尔，Scripps研究所）；项目4，“造血过程中C/EBP α的调节”（项目负责人：Daniel G. Tenen，哈佛医学院贝斯以色列女执事医疗中心）。行政核心将负责项目的许多互动功能，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。

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.