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: 7442126
• 负责人: JONATHAN S BERG
• 金额: $ 5.67万
• 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/7442126
• 关键词: Affect; Animal Model; Biochemistry; Biological Assay; Cell Cycle; Cell Proliferation; Cell physiology; Cell surface; Cells; Chromatin; Chromatin Structure; Commit; Condition; Cultured Cells; Development; Disease; Embryonic Development; Engraftment; Epigenetic Process; Flow Cytometry; Fluorescence Microscopy; Fluorouracil; Gene Expression; Gene Expression Profiling; Gene Expression Regulation; Genes; Genetic; Hematopoiesis; Hematopoietic; Hematopoietic System; Hematopoietic stem cells; Histone Deacetylation; Hypersensitivity; In Vitro; Investigation; Life Cycle Stages; Methylation; Modeling; Modification; Molecular Biology Techniques; Mus; Pattern; Personal Satisfaction; Phenotype; Play; Population; Regenerative Medicine; Regulation; Research; Role; Staging; Stem cells; Study models; Testing; Time; body system; cell type; chromatin immunoprecipitation; clinical application; day; gene therapy; inhibitor/antagonist; interest; mouse model; research study; self-renewal

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.

造血干细胞（HSC）在再生医学中的潜在应用引起了极大的兴趣 和基因治疗。尽管转录谱已经开始阐明 HSC 的遗传调控 静止和增殖，新出现的证据表明表观遗传调控可能发挥重要作用 在造血系统发育中的作用。这里提出的调查路线将拓宽我们的范围 了解 HSC 自我表达过程中控制基因表达的表观遗传机制 更新和差异化。该提案的核心部分将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、 荧光显微镜和药理学干扰来研究这些假设。什么时候 完成后，这项研究将有助于更好地了解 HSC 中基因表达的调控 和分化的造血细胞，并能够在体外操作这些细胞，作为朝着这一目标迈出的一步 扩大 HSC 群体以用于基因治疗的临床应用。

项目成果

International Evidence Based Reappraisal of Genes Associated With Arrhythmogenic Right Ventricular Cardiomyopathy Using the Clinical Genome Resource Framework.

• DOI: 10.1161/circgen.120.003273
• 发表时间: 2021-06
• 期刊: Circulation. Genomic and precision medicine
• 作者: James CA;Jongbloed JDH;Hershberger RE;Morales A;Judge DP;Syrris P;Pilichou K;Domingo AM;Murray B;Cadrin-Tourigny J;Lekanne Deprez R;Celeghin R;Protonotarios A;Asatryan B;Brown E;Jordan E;McGlaughon J;Thaxton C;Kurtz CL;van Tintelen JP
• 通讯作者: van Tintelen JP