Epigenetic control of gene expression in hematopoiesis

造血干细胞(HSCs)在再生医学中具有广阔的应用前景 和基因疗法。尽管转录图谱已经开始阐明HSC的基因调控 停滞和增殖，新出现的证据表明，表观遗传调控可能起到重要作用 在造血系统发育中的作用。这里提出的调查范围将扩大我们的 造血干细胞自我调控基因表达的表观遗传学机制 更新和差异化。该提案的中心部分将同时使用细胞培养和动物模型。 为了研究这些问题，我计划使用分子生物学、生物化学、流式细胞术、 荧光显微镜和药物干预来研究这些假说。什么时候 这项研究完成后，将更好地了解造血干细胞中基因表达的调控。 和分化的造血细胞，并能够在体外操纵这些细胞，作为迈向 扩大造血干细胞群体用于基因治疗的临床应用。

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.