Xenotransplant and Genome Editing Core

摘要 转基因动物和免疫功能低下的动物是研究该疾病的金标准模型 正常发育和疾病背景下造血细胞的分子调控，以及 开发基于干细胞的新型治疗方式，用于多种非恶性血液病 失调。血液学研究的未来还在于我们检查造血细胞功能的能力 单细胞水平并将单细胞行为与转录组和表观遗传分析相关联。中华基督教会 异种移植和基因组编辑核心 (XGEC) 是一个成熟、高效和创新的核心 旨在提供专门的小鼠品系、各种动物服务，以提高效率和 及时且具有成本效益的细胞移植测定标准化和转基因动物服务 为 CCHSCC 会员打造时尚。总体假设是，提供集中式核心服务 CCHSCC 成员的大量鼠标需求将提高有效性、及时性、成本效益和 科学研究的整体影响，从而加速血液病的发现和治疗 疾病。 与外部供应商相比，XGEC 以具有成本效益的方式提供专门的小鼠品系， 包括一系列免疫缺陷小鼠品系（即 NSG、NSG-3GM3、NRG-SGM3、Rag-/-gc-/- /WvWv 和 B6.BoyJ) 用于人类造血细胞异种移植，用于临床前研究 关于人类和小鼠造血干细胞的基因转移，用于人类造血干细胞 和单细胞植入研究，以及定量（竞争性）造血干细胞植入 研究（目标 1）。 XGEC 进一步提供专门的动物服务，允许群体和单细胞 移植检测，包括动物照射和细胞移植服务（目标 2）以及动物 操纵和监控服务（目标 3）。此外，XGEC 还提供生成 转基因和转基因小鼠品系（目标 4）。自从开始提供 CRISPR-Cas 服务以来 2014年3月，核心已经为CCHMC研究人员和其他人生成了工程动物模型 中心和更广泛的研究界。最后，XGEC提供技术支持并促进 体内研究的综合设计和分析的研究合作（目标 5）。这些服务将 促进参与 CCCEH 的研究人员之间的专业知识共享并促进互动， 并将在未来吸引新的核心用户。总体而言，XGEC 提供独特的动物服务组合 并由训练有素的人员在博士的监督下进行集中的专业知识。斯塔奇诺夫斯基 和黄以具有成本效益和标准化的方式，从而提供最先进的非 恶性分子血液学。这些服务将支持新治疗方式的开发 （药理学和基于细胞的）和转化 I 期和 II 期研究。

Abstract Genetically modified and immunocompromised animals are the gold-standard models for investigating the molecular regulation of hematopoietic cells in the context of normal development and diseases, and for the development of novel stem cell-based therapeutic modalities for a wide variety of non-malignant hematological disorders. The future of hematology research also lies in our ability to examine hematopoietic cell function at single cell level and correlate single cell behavior with transcriptome and epigenetic profiling. The CCCEH Xenotransplant and Genome Editing Core (XGEC) is an established, productive and innovative core designed to provide specialized mouse strains, a wide variety of animal services for efficiency and standardization of cell transplantation assays, and transgenic animal services in a timely and cost effective fashion to members of the CCHSCC. The overarching hypothesis is that a centralized core service providing the myriad mouse needs of CCHSCC members will enhance the effectiveness, timeliness, cost-efficiency and overall impact of the scientific research and thereby accelerate the discovery and treatment of hematological diseases. XGEC provides specialized mouse strains in a cost effective manner compared with external vendors, including a collection of immunodeficient mouse strains (i.e., NSG, NSG-3GM3, NRG-SGM3, Rag-/-gc-/- /WvWv, and B6.BoyJ) utilized for xenotransplantation of human hematopoietic cells, for preclinical studies concerning gene transfer in humans and mouse hematopoietic stem cells, for human hematopoietic stem cell and single cell engraftment studies, and for quantitative (competitive) hematopoietic stem cell engraftment studies (Aim 1). The XGEC further provides specialized animal services allowing for population and single cell transplantation assays, including animal irradiation and cell transplantation services (Aim 2), and animal manipulation and monitoring services (Aim 3). In addition, the XGEC offers all services for the generation of transgenic and genetically–modified mouse lines (Aim 4). Since it began offering CRISPR-Cas services in March 2014, the core has already generated engineered animal models to CCHMC investigators and among Centers and within the wider research community. Lastly, XGEC provides technical support and facilitates research collaborations for comprehensive design and analysis of in vivo studies (Aim 5). These services will facilitate the sharing of expertise and promote interaction between investigators participating in the CCCEH, and will attract new core users in the future. Overall, the XGEC offers a unique combination of animal services and concentrated expertise performed by well-trained personnel under the supervision of Drs. Starczynowski and Huang in a cost effective and standardized way, thereby providing state-of-the-art investigation of non- malignant molecular hematology. These services will support the development of new therapeutic modalities (pharmacological and cell-based) and translational Phase I and II studies.