GENETIC ANALYSIS OF GERM CELL FORMATION

生殖细胞形成的遗传分析

• 批准号: 7715918
• 负责人: SHOUKHRAT M MITALIPOV
• 金额: $ 6.67万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7715918
• 关键词: Cell Lineage; Chromosome Mapping; Code; Computer Retrieval of Information on Scientific Projects Database; Down-Regulation; ES Cell Line; Embryo; Funding; Germ Cells; Geron H14 stem cell line; Grant; Human; Human Genetics; In Vitro; Infertility; Institution; Purpose; Research; Research Personnel; Resources; Source; Specific qualifier value; System; Transplantation; UC01; United States National Institutes of Health; WA01 cell line; Wisconsin H14 stem cell line; Y Chromosome; genetic analysis; human embryonic stem cell; human embryonic stem cell line; human male; in vivo; male; men; nonhuman primate; stem

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Germ cells can be specified and differentiated from human embryonic stem (ES) cells. Thus, we hypothesize that the human ES cell system can be used to specifically probe the genetics of human germ cell formation and differentiation. Moreover, we hypothesize that the downregulation of key genes that map to a region of the Y chromosome that is commonly deleted in infertile men, the AZFc region, will abolish the ability to form and/or differentiate human male germ cells in vitro and in vivo in a transplant system. To explore this hypothesis, we propose to: 1) Characterize the ability of NIH-approved human ES cell lines to contribute to the germ cell lineage in vitro and in vivo. For this purpose, we will use ES cell lines H1, H14 and HSF1 (NIH codes: WA01, WA14 and UC01). 2) Silence the Y chromosome genes that map to the AZFc deletion interval and assess germ cell formation in vitro. 3) Silence the Y chromosome genes that map to the AZFc deletion interval and assess the ability of germ cells to colonize nonhuman primate spermatogenic tubules and subsequently differentiate. The ability of human ES derived male germ cells to colonize nonhuman primate spermatogenic tubules will be the focus of research conducted at ONPRC.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 生殖细胞可以被特异化并与人类胚胎干（ES）细胞区分开来。 因此，我们假设人类 ES 细胞系统可用于特异性探测人类生殖细胞形成和分化的遗传学。 此外，我们假设，映射到不育男性中通常缺失的 Y 染色体区域 AZFc 区域的关键基因的下调，将消除移植系统中体外和体内形成和/或分化人类男性生殖细胞的能力。 为了探索这一假设，我们建议：1）表征 NIH 批准的人类 ES 细胞系在体外和体内促进生殖细胞谱系的能力。 为此，我们将使用 ES 细胞系 H1、H14 和 HSF1（NIH 代码：WA01、WA14 和 UC01）。 2) 沉默映射到 AZFc 缺失区间的 Y 染色体基因并评估体外生殖细胞的形成。 3) 沉默映射到 AZFc 缺失区间的 Y 染色体基因，并评估生殖细胞定植非人灵长类生精小管并随后分化的能力。 人类 ES 衍生的雄性生殖细胞定殖非人类灵长类生精小管的能力将成为 ONPRC 的研究重点。