Genetics of Directed Embryonic Stem Cell Differentiation

胚胎干细胞定向分化的遗传学

• 批准号: 7481347
• 负责人: Ted Choi
• 金额: $ 44.72万
• 依托单位: PREDICTIVE BIOLOGY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-06-01 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7481347
• 关键词: American; Biology; Cardiac Myocytes; Cardiomyoplasty; Cell Differentiation process; Cells; Cellular Morphology; Cessation of life; Clinic; Collaborations; Condition; Coronary heart disease; Detection; Disease; ES Cell Line; Embryo; Evaluation; Eye; Genes; Genetic; Genetic Determinism; Genetic Screening; Genetic Variation; Genome; Genome Scan; Government; Health Care Costs; Heart; Heart Diseases; Institution; Laboratories; Measures; Mus; Persons; Pharmacologic Substance; Phase; Production; Property; Public Health; Purpose; Quantitative Trait Loci; Regenerative Medicine; Stem cells; System; Therapeutic; base; cell type; embryonic stem cell; genetic analysis; heart cell; novel strategies; repaired; stem

DESCRIPTION (provided by applicant): Repair of the damaged heart using cardiomyocytes derived from embryonic stem cells is a promising avenue for treatment of heart disease. Many fundamental questions about stem cell differentiation and cardiomyoplasty must be answered before that promise is realized in the clinic. We propose to develop a broadly applicable, cell based system to identify genetic factors involved in the directed differentiation of ES cells to cardiomyocytes. In Phase I we will determine the feasibility of this system by establishing a panel of ES cell lines from F2 embryos of one strain-pair, measuring the extent of differentiation to cardiomyocytes under defined culture conditions, and conducting a statistical analysis for quantitative trait loci (QTL) for differentiation to cardiomyocytes. The aim of Phase I is to demonstrate that the proposed ES cell panel can identify subchromosomal regions of the genome harboring one or more genes involved in differentiation of ES cells. In Phase II, F2 ES lines from additional strain-pairs will be established and, in conjunction with a panel of F1 ES cells, used to screen for genetic determinants of directed differentiation under a variety of culture conditions. The platform will be commercialized through strategic alliances with pharmaceutical and biotech companies, as well as in collaborations with academic institutions. PUBLIC HEALTH RELEVANCE: Over 13 million Americans are afflicted with coronary heart disease each year, leading to half a million deaths and healthcare costs in excess of fifty billion dollars. Using stem cells to repair the damaged heart is a promising new approach to treat a disease with very few treatment options. This project will aid in this approach by building a genetic system to identify the factors that influence production of heart cells from embryonic stem cells.

描述（由申请人提供）：使用源自胚胎干细胞的心肌细胞修复受损的心脏，是治疗心脏病的有前途的途径。在诊所实现诺言之前，必须回答有关干细胞分化和心肌成形术的许多基本问题。我们建议开发一种基于细胞的广泛适用的系统，以鉴定ES细胞向心肌细胞的定向分化涉及的遗传因素。在第一阶段，我们将通过从一个应变对的F2胚胎中建立一系列ES细胞系来确定该系统的可行性，从而在定义的培养条件下测量与心肌细胞的分化程度，并对定量性状基因座（QTL）进行统计分析，以分化与心肌细胞的分化。第一阶段的目的是证明所提出的ES细胞图可以鉴定出具有与ES细胞分化有关的一个或多个基因的基因组的亚染色体区域。在II阶段，将建立来自其他应变对的F2 ES线，并与F1 ES细胞的一组结合，用于筛选在各种培养条件下定向分化的遗传决定因素。该平台将通过与制药和生物技术公司以及与学术机构合作的战略联盟进行商业化。公共卫生相关性：每年超过1300万美国人患有冠心病，导致50万人死亡和医疗保健费用超过50亿美元。使用干细胞修复受损的心脏是一种有希望的新方法，可以使用很少的治疗选择来治疗疾病。该项目将通过建立遗传系统来确定影响胚胎干细胞产生心脏细胞的因素，从而有助于这种方法。