A National Resource for Lung disease-specific iPS cells

描述（由申请人提供）：该提案旨在为肺部研究人员建立一个正式的国家资源，包括一个肺部疾病特异性诱导多能干细胞（iPSC）库，可以无限制或排他性地共享。超过200个与人类肺部疾病相关的iPSC克隆及其基因编辑后代目前存放在波士顿大学/波士顿医学中心的再生医学中心（CReM），为任何基础科学家提供了前所未有的机会，以获得取之不尽的患者来源的肺上皮细胞，血管细胞，免疫细胞或间质细胞。这些细胞含有 每个患者自身的遗传背景现在可用于体外人类肺部疾病建模、个性化疗法的药物筛选以及未来基于肺再生细胞的疗法的开发。该库中最有价值的人类克隆不仅携带最常见的肺部疾病诱导突变（例如编码CFTR、Alpha-1抗胰蛋白酶、BMPR 2、SPC、SPB、ABCA 3和NKX2.1的基因座突变），还携带通过最先进的基因编辑技术靶向特定基因座的敲入荧光染料报告基因。平行地，该库还包括从转基因或敲入小鼠产生的50个小鼠iPSC克隆，其携带肺谱系的充分表征的荧光染料报告物（SPC-GFP、T1 a-GFP、Tie 2-GFP、SMA-GFP和Nkx2.1-GFP）。我们建议通过四个具体目标来建立这个细胞库，以实现以下目标： B）建立质量保证途径和方法，用于储存携带大多数美国肺研究人员在未来几年所需的最常见基因突变和肺谱系报告基因的详尽的人类和小鼠系组，c）制定正式的教育和培训计划，能够在全国范围内传播充分利用这些新工具并将其区分为肺谱系所需的专业知识，以及d）在财务、后勤和教育方面自我维持银行。

DESCRIPTION (provided by applicant): This proposal seeks to estabalish a formalized national resource for lung researchers consisting of a lung disease-specific induced pluripotent stem cell (iPSC) bank that can be shared without restriction or exclusivity. More than 200 human lung disease-relevant iPSC clones, and their gene-edited progeny, are now banked in the Center for Regenerative Medicine (CReM) of Boston University/Boston Medical Center, providing an unprecedented opportunity for any basic scientist to derive an inexhaustible supply of patient-derived lung epithelial, vascular, immune, or interstitial cells. These cells containing each patient's own genetic background are now available for in vitro human lung disease modeling, drug screening of personalized therapeutics, and the development of future lung regeneration cell-based therapies. The most valuable human clones in this bank not only carry the most common lung disease-inducing mutations (e.g. mutations in loci encoding CFTR, Alpha-1 antitrypsin, BMPR2, SPC, SPB, ABCA3, and NKX2.1), but also carry knock-in fluorochrome reporters targeted to specific loci through state-of-the-art gene editing technologies. In parallel, the bank also includes 50 mouse iPSC clones generated from transgenic or knock-in mice that carry well characterized fluorochrome reporters of lung lineages (SPC-GFP, T1a-GFP, Tie2-GFP, SMA-GFP, and Nkx2.1-GFP). We propose to establish this cell bank through four specific aims to accomplish the goals of: a) national sharing of iPSCs that comprise a critical resource in high demand by both basic and clinical lung researchers, b) establishment of quality assurance approaches and methods for banking an exhaustive panel of human and mouse lines carrying the most common gene mutations and lung lineage reporter genes required by the majority of U.S. lung researchers in the years ahead, c) development of a formalized education and training program able to nationally disseminate the expertise required to fully harness these new tools and differentiate them into lung lineages, and d) self-sustained maintenance of the bank financially, logistically, and educationally.