Epigenetic control of gene expression in hematopoiesis

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具有潜在的应用前景。尽管转录谱分析已经开始阐明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。本文提出的研究方向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。一旦完成，这项研究将提供对造血干细胞和分化造血细胞基因表达调控的更好理解，并使这些细胞在体外操作成为扩大造血干细胞群体用于基因治疗临床应用的一步。

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.