Xenotransplant and Genome Editing Core

摘要 转基因和免疫受损动物是研究 在正常发育和疾病的背景下，造血细胞的分子调控，以及 以干细胞为基础的多种非恶性血液病治疗方法的发展 精神错乱。血液学研究的未来还在于我们有能力在 单细胞水平并将单细胞行为与转录组和表观遗传学特征相关联。CCCEH 异种移植和基因组编辑核心(XGEC)是一个成熟的、多产的和创新的核心 旨在提供专门的老鼠品系，各种动物服务，以提高效率和 标准化细胞移植检测，及时、经济高效地提供转基因动物服务 为CCHSCC成员提供时尚。最重要的假设是，一个集中的核心服务提供 CCHSCC成员的无数鼠标需求将增强有效性、及时性、成本效益和 全面影响科学研究，从而加快血液病的发现和治疗 疾病。 与外部供应商相比，XGEC以经济高效的方式提供专门的小鼠品系， 包括免疫缺陷小鼠品系的集合(即，NSG、NSG-3GM3、NRG-SGM3、RAG-/-GC-/- /WvWv和B6.BoyJ)用于人造血细胞的异种移植，用于临床前研究 关于人和小鼠造血干细胞的基因转移，人造血干细胞 和单细胞移植研究，以及定量(竞争性)造血干细胞移植 研究(目标1)。XGEC还提供专门的动物服务，允许种群和单细胞 移植试验，包括动物照射和细胞移植服务(目标2)和动物 操纵和监测服务(目标3)。此外，XGEC提供所有服务，以产生 转基因和转基因小鼠品系(目标4)。自#年开始提供CRISPR-CAS服务以来 2014年3月，该核心已经向CCHMC调查人员和 中心和更广泛的研究社区内。最后，XGEC提供技术支持和便利 为体内研究的综合设计和分析进行研究协作(目标5)。这些服务将 促进分享专门知识，促进参加CCCEH的调查人员之间的互动， 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斯塔奇诺夫斯基博士的监督下提供集中的专业知识 和黄以经济高效和标准化的方式，从而提供最先进的非 恶性分子血液病。这些服务将支持开发新的治疗方式。 (药理学和基于细胞的)和翻译阶段I和II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.