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发挥着关键作用，其中最重要的是造血干细胞（HSC）定向的控制。了解这一过程对于理解 HSC 功能和自我更新至关重要，这种理解将为治疗目的操纵 HSC 以及了解涉及 HSC 的疾病过程（包括白血病）带来新的见解。最后，对 HSC 承诺的理解的进展将成为理解其他类型干细胞的模型。该计划名为“造血干细胞承诺”，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。其中包括：项目1：“造血干细胞承诺的分支点”（项目负责人：Koichi Akashi，哈佛医学院达纳法伯癌症研究所；项目2：“造血干细胞中的信号转导机制”（项目负责人：Roger J） . Davis，马萨诸塞大学医学中心，伍斯特）；项目 3：“造血干细胞中的 Runx1”（项目负责人：Dong-Er 张，斯克里普斯）；研究所）；以及项目 4，“造血过程中 C/EBP α 的调节”（项目负责人：哈佛医学院贝斯以色列女执事医疗中心的 Daniel G. Tenen）。计划，包括定期会议、研讨会和项目之间的交流。生物统计学核心将为统计设计和分析提供指导。 公共健康相关性：通过结合多种方法，包括转录调控、信号转导以及基因敲除和敲入小鼠的研究，我们将提供有关干细胞功能调控的有价值的新信息。