Penn integrated Human Pancreas procurement and Analysis Program

宾夕法尼亚大学综合人类胰腺采购和分析计划

• 批准号: 9236460
• 负责人: Michael R Betts
• 金额: $ 1224.96万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-20 至 2021-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9236460
• 关键词: Acinar Cell; Adolescent; Age; Archives; Autoantibodies; B cell repertoire; B-Lymphocytes; Beta Cell; Bioenergetics; Biology; Blood; CD8B1 gene; Calcium; Cell Line; Cell surface; Cells; Chromatin; Collaborations; Communities; Core Facility; Cyclic GMP; Cytometry; DNA; Data; Data Analyses; Data Set; Databases; Deposition; Derivation procedure; Diabetes Mellitus; Diagnosis; Effector Cell; Endocrine system; Enhancers; Epigenetic Process; Etiology; Fibroblasts; Flow Cytometry; Frequencies; Functional disorder; Future; Genomics; Genotype; Glucagon; Human; Hyperinsulinism; Image; Image Analysis; Imaging technology; Immune; Immune system; Immunobiology; Immunologics; Insulin; Insulin-Dependent Diabetes Mellitus; Ions; Islet Cell; Islets of Langerhans; Maps; Measurement; Medical History; Medical Records; Membrane Potentials; Memory; Metadata; Modality; Molecular Profiling; Natural History; Non-Insulin-Dependent Diabetes Mellitus; Organ Donor; Oxygen Consumption; Pancreas; Patients; Pennsylvania; Phenotype; Physiological; Population; Process; Proteins; Recording of previous events; Research Infrastructure; Research Personnel; Resolution; Resources; Review Committee; Risk; Sampling; Slide; Sorting - Cell Movement; Source; Spleen; Staining method; Stains; T-Lymphocyte; T-Lymphocyte Subsets; Technology; Tissues; Universities; Work; abstracting; base; biobank; cell type; combinatorial; cost; data access; data integration; data sharing; data visualization; epigenomics; experience; human leukocyte antigen testing; human tissue; induced pluripotent stem cell; islet; lymph nodes; member; mitochondrial membrane; next generation sequencing; novel; programs; protein biomarkers; quantitative imaging; tissue processing; transcriptome sequencing; two-dimensional

Penn Human Pancreas Procurement and Analysis Program Abstract Utilizing our existing infrastructure and scientific collaborations, we have assembled 6 cores with expertise ranging from pancreas procurement and islet isolation to data integration for a comprehensive and integrated Human Pancreas Procurement and Analysis Program based at the University of Pennsylvania. Core A will procure a spectrum of human pancreata and detailed donor medical history; perform high resolution HLA typing by next generation sequencing; isolate islets; and distribute islets and tissues to the other Cores for further analysis or processing. Core B will perform physiological phenotyping on the isolated islets. Core C will quantify and characterize memory T cell subsets by flow cytometry and single cell qPCR analysis; characterize suppressive activity of Tregs and the ability of related effector cells to be suppressed; B cell phenotyping; and generate chromatin accessibility maps of enhancers in pathogenic cell types. Core D will perform multiple advanced modalities for the molecular profiling of isolated islets including RNAseq and microRNAseq of sorted islet cell populations; mass cytometry for single cell quantification of more than 20 cell surface and intracellular markers; and single cell RNAseq. Core E will process tissues using multiple modalities that will allow for analysis using advanced technologies such as multiplexed immunoflourescent staining, combinatorial barcoded FISH (combFISH), whole slide imaging, and quantitative image analysis of protein markers and immune cell infiltrates. This Core will adapt 2-dimensional mass cytometry to pancreatic sections utilizing multiplexed ion beam imaging (MIBI) technology. This Core will also archive tissues as well as DNA and blood, and facilitate sample distribution to HPPAP approved researchers. Finally, Core F will assemble, annotate and maintain an open access database for the Program and its member-researchers, and collaborate with the HIRN in the sharing of data from both programs. The entire Program will be executed by an Administrative Core consisting of the PIs, with assistance from an Executive Committee consisting of the core leaders. The Administrative Core will interface with an external committee to review applications for HPPAP biosample use, and will collaborate with the HIRN. The Program will also interact with the HPPAP member/PANC DB user community to provide a richly annotated source of physiologic, genomic and immunologic data on the tissue-based landscape governing T1D.

宾夕法尼亚人胰腺采购和分析计划 抽象的 利用我们现有的基础设施和科学合作，我们与 专业知识从胰腺采购和胰岛隔离到数据集成 基于全面和集成的人类胰腺采购和分析计划 宾夕法尼亚大学。核心A将获得一系列人类胰腺和 详细的供体病史；下一代执行高分辨率HLA打字 测序；分离胰岛；并将胰岛和组织分配到其他核心以进行进一步分析 或处理。核心B将对分离的胰岛进行生理表型。 Core C Will 通过流式细胞仪和单细胞QPCR量化和表征记忆T细胞子集 分析;表征Treg的抑制活性和相关效应细胞的能力 被压制； B细胞表型；并生成增强剂的染色质可访问性图 致病细胞类型。核心D将对分子执行多种高级方式 分类胰岛细胞种群在内的分离胰岛和包括microRNaseq的分析； 质量细胞仪，用于单细胞定量20个以上细胞表面和细胞内 标记；和单细胞RNASEQ。核心E将使用多种方式处理组织 允许使用高级技术（例如多路复用免疫氟）进行分析 染色，组合条形码鱼（梳子鱼），整个幻灯片成像和定量图像 分析蛋白质标志物和免疫细胞浸润。该核心将适应二维 利用多路复用离子束成像（MIBI）技术的胰岛细胞仪到胰腺切片。 该核心还将存档组织以及DNA和血液，并促进样品分布 为HPPAP批准的研究人员。最后，核心F将组装，注释和保持开放 访问该计划及其成员研究人员的数据库，并与Hirn合作 来自两个程序的数据共享。整个程序将由 在执行委员会的协助下，由PI组成的行政核心 由核心领导者组成。行政核心将与外部委员会接口 审查HPPAP BioSample使用的应用程序，并将与Hirn合作。这 程序还将与HPPAP成员/PANC DB用户社区进行互动，以提供 关于基于组织的生理，基因组和免疫学数据的丰富注释来源 景观管理T1D。