Ground state rabbit pluripotent stem cells

基态兔多能干细胞

• 批准号: 9345184
• 负责人: Qilong Ying
• 金额: $ 22.58万
• 依托单位: ATGC, INC.
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2019-01-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9345184
• 关键词: Adult; Age; Animals; Biological Models; Biomedical Research; Body Size; Breeding; CRISPR/Cas technology; Cell Line; Cells; Chimera organism; Clustered Regularly Interspaced Short Palindromic Repeats; Communities; Derivation procedure; Distal; Embryo; Embryology; Enhancers; Gene Targeting; Generations; Genes; Genetic Enhancer Element; Germ Cells; Goals; Human; In Vitro; Infant; Injection of therapeutic agent; Inner Cell Mass; Longevity; Methods; Modeling; Mus; Mutation; Operative Surgical Procedures; Oryctolagus cuniculus; Pathway interactions; Phase; Play; Pluripotent Stem Cells; Pregnancy; Process; Production; Property; Rattus; Recipe; Reporter; Reporting; Research; Role; Stem cells; System; Technology; Testing; Therapeutic; Time; Translational Research; Work; base; blastocyst; clinically relevant; embryonic stem cell; genetic signature; human disease; human embryonic stem cell; human pluripotent stem cell; human stem cells; improved; induced pluripotent stem cell; knockin animal; novel; nuclease; organ regeneration; safety testing; small molecule; small molecule libraries; stem cell biology; success; tool; transmission process

Abstract To evaluate the therapeutic applications of stem cells, it is essential to develop translational research using several animal species. Rabbit is a useful model for biomedical research. It has been used to study a number of human diseases. Compared to mice, rabbits have a more similar embryology and stem cell biology to those of humans, an adult body size comparable to human infants that allows for practical surgical procedures, and a longer lifespan to permit a clinically relevant research time. It will be beneficial to establish rabbit pluripotent stem cell (PSC) lines as a non-murine model system for better understanding human stem cells, and for testing the safety and efficacy of new stem cell based technologies. The availability of ground state rabbit ESCs in the age of gene editing is expected to create many novel research tools for translational research community. Pluripotent rabbit embryonic stem cells (rbESCs) and induced pluripotent stem cells (iPSCs) have been reported. However, these cells share typical properties of primed stem cells, and all failed to transmit to the germ cells. The ground state or germline transmitting ESCs and iPSCs are only reported in mice and rats. It remains to be tested whether ground state ESCs exist in non-rodent species. The PI of this project made the breakthrough in establishing the first non-murine ground state ESCs in rats. Here we propose to derive ground state rbESCs. In Aim 1, we will establish an Oct4-ΔPE-GFP reporter cell line, which would express green florescent in ground state but not in prime state. In Aim 2, we will screen small molecule library to identify compounds that are beneficial for the ground state in rabbit ESCs. In Aim 3, we will derive new ground state rabbit ESCs.

抽象的 为了评估干细胞的治疗应用，必须使用 几种动物。兔子是生物医学研究的有用模型。它已被用来研究一个数字 人类疾病。与小鼠相比，兔子具有与那些更相似的胚胎学和干细胞生物学 人类，一种与人类婴儿相当的成年体型，可以进行实际的外科手术，并且 更长的寿命可以允许临床相关的研究时间。建立兔多能是有益的 干细胞（PSC）线作为一种非熔融模型系统，以更好地理解人类干细胞，并用于测试 新的基于干细胞的技术的安全性和效率。地面兔子的可用性在 基因编辑的年龄有望为转化研究社区创建许多新颖的研究工具。 多能兔胚胎干细胞（RBESC）和诱导的多能干细胞（IPSC）已是 报告。但是，这些细胞具有尖锐的干细胞的典型特性，并且都无法传播到 生殖细胞。仅在小鼠和大鼠中报告了ESC和IPSC的基态或种系。它 尚待测试是否存在于非变形物种中的基态ESC。 该项目的PI取得了突破性的突破性，即建立大鼠的第一个非摩rine基态ESC。 在这里，我们建议得出基态RBESC。在AIM 1中，我们将建立一个OCT4-ΔPE-GFP报告基池 线，这将在基态下表达绿色的荧光，但不能在主要状态下表达绿色。在AIM 2中，我们将筛选小 分子库鉴定对兔子ESC中基态有益的化合物。在AIM 3中，我们将 得出新的地面兔子逃脱。