Epigenetic control of gene expression in hematopoiesis

造血过程中基因表达的表观遗传控制

• 批准号: 7155937
• 负责人: JONATHAN S BERG
• 金额: $ 5.8万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-11-01 至 2008-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7155937
• 关键词: bone marrow transplantation; cell differentiation; cell growth regulation; cell proliferation; chromatin; chromatin immunoprecipitation; developmental genetics; epigenetics; flow cytometry; fluorescence microscopy; fluorouracil; gene expression profiling; genetic promoter element; genetic regulation; genetic transcription; genetically modified animals; hematopoiesis; hematopoietic stem cells; laboratory mouse; microarray technology; phenotype; postdoctoral investigator; tissue /cell culture

DESCRIPTION (provided by applicant): Hematopoietic stem cells (HSCs) are of great interest for potential applications in regenerative medicine and gene therapy. Although transcriptional profiling has begun to elucidate genetic regulation of HSC quiescence and proliferation, emerging evidence suggests that epigenetic regulation may play an important role in development of the hematopoietic system. The lines of investigation proposed here will broaden our understanding of the epigenetic mechanisms controlling gene expression in HSCs as they undergo self- renewal and differentiation. The central portion of this proposal will use both cell culture and animal models to study these questions and I plan to use techniques from molecular biology, biochemistry, flow cytometry, fluorescence microscopy, and pharmacologic interference to investigate these hypotheses. When completed, this research will provide a better understanding of the regulation of gene expression in HSCs and differentiated hematopoietic cells and enable manipulation of these cells in vitro as a step toward expansion of HSC populations for clinical applications in gene therapy.

描述（由申请人提供）：造血干细胞（HSC）在再生医学和基因治疗中的潜在应用引起了人们的极大兴趣。虽然转录谱已经开始阐明HSC静止和增殖的遗传调控，但新出现的证据表明，表观遗传调控可能在造血系统的发育中发挥重要作用。本文提出的研究思路将拓宽我们对造血干细胞自我更新和分化过程中控制基因表达的表观遗传机制的理解。本提案的核心部分将使用细胞培养和动物模型来研究这些问题，我计划使用分子生物学、生物化学、流式细胞术、荧光显微镜和药理学干扰等技术来研究这些假设。当完成后，这项研究将提供一个更好的理解调控的基因表达的HSC和分化的造血细胞，并使这些细胞在体外的操作，作为一个步骤，扩大HSC群体的临床应用在基因治疗。