Ground state rabbit pluripotent stem cells

摘要 为了评估干细胞的治疗应用，必须利用 几种动物物种。兔是生物医学研究的一种有用模型。它被用来研究一些 人类疾病。与小鼠相比，兔子的胚胎学和干细胞生物学与小鼠更相似。 成人的身体大小与人类婴儿相当，允许进行实际的外科手术， 更长的寿命，以允许临床相关的研究时间。这将有利于建立兔多能性 干细胞（PSC）系作为非鼠模型系统，用于更好地了解人类干细胞， 新的干细胞技术的安全性和有效性。基态兔胚胎干细胞的可用性 基因编辑时代有望为翻译研究界创造许多新的研究工具。 多能兔胚胎干细胞（rbESC）和诱导多能干细胞（iPSC）已经被研究。 报道然而，这些细胞具有引发的干细胞的典型特性，并且都未能转移到 生殖细胞基态或生殖系传输ESC和iPSC仅在小鼠和大鼠中报道。它 在非啮齿类物种中是否存在基态ESC仍有待测试。 本项目的主要研究成果是首次在大鼠体内建立了非鼠源性基态胚胎干细胞。 在这里，我们建议获得基态rbESCs。目的一：建立Oct 4-ΔPE-GFP报告细胞 线，其将在基态但不在主要状态下表示绿色荧光。在目标2中，我们将屏幕缩小 分子库，以确定有利于兔ESC基态的化合物。在目标3中，我们 获得新的基态兔ESC。

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.