The Human Pancreas Analysis Program for Type 2 Diabetes

2 型糖尿病人类胰腺分析项目

• 批准号: 10261669
• 负责人: KLAUS H KAESTNER
• 金额: $ 94万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-23 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10261669
• 关键词: ATAC-seq; Adipose tissue; Adolescent; Architecture; Archives; Bioenergetics; Biological Assay; Biology; Biopsy; Blood; Calcium; Cell physiology; Cell surface; Cells; Collaborations; Colon; Communities; Cyclic GMP; Cytometry; DNA; Data; Data Analyses; Data Set; Databases; Diabetes Mellitus; Diagnosis; Disease; Duodenum; Epidemic; Epithelial Cells; Etiology; Funding; Future; Genetic; Genomic DNA; Genomics; Glucagon; Glucose; Heterogeneity; Histologic; Hour; Human; Image; Inflammatory Response; Infrastructure; Insulin; Insulin-Dependent Diabetes Mellitus; Intestines; Investigation; Islet Cell; Islets of Langerhans; Knowledge; Leadership; Liver; Lymphocyte; Measurement; Medical History; Medical Records; Metabolic; Metadata; Modality; Molecular Profiling; Mutation; National Institute of Diabetes and Digestive and Kidney Diseases; Natural History; Non obese; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Organ; Organ Donor; Organ Procurements; Oxygen Consumption; PTPRC gene; Pancreas; Patients; Pennsylvania; Phenotype; Physiological; Population; Process; Protein Analysis; Proteins; Publications; Recording of previous events; Research Personnel; Resolution; Skeletal Muscle; Somatostatin; Stains; Technology; Tissues; United States National Institutes of Health; Universities; Visualization; Work; base; biobank; data access; data integration; data resource; data sharing; data submission; data visualization; epigenomics; experience; human leukocyte antigen testing; human tissue; islet; maturity onset diabetes of the young; member; methylome; molecular phenotype; morphometry; multidimensional data; next generation sequencing; programs; protein biomarkers; quantitative imaging; response; sample fixation; single-cell RNA sequencing; transcriptome; transcriptome sequencing; whole slide imaging

Penn Human Pancreas Analysis Program – T2D Abstract Building on our existing infrastructure and scientific collaborations, and the expertise gained during the first two years of the HPAP effort for Type 1 Diabetes, we have assembled five cores with expertise ranging from pancreas procurement and islet isolation to data integration. These Cores form a for a comprehensive and integrated Penn Human Pancreas Analysis Program – T2D based entirely 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 perform multiple advanced modalities for the molecular profiling of isolated islets including RNAseq, ATACseq and DNA methylome analysis of sorted islet cell populations; single cell ATACseq and RNAseq, and mass cytometry for single cell quantification of more than 20 cell surface and intracellular markers. Core D will process tissues using multiple modalities that will allow for analysis using advanced technologies such as multiplexed immunoflourescent staining, whole slide imaging, and imaging mass cytometry. This Core will also archive tissues, DNA and blood, as well as other T2D-relevant organs such as skeletal muscle, intestine, adipose tissue and liver for future use by other NIDDK-approved consortia. Finally, Core E 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 directed by an Executive Committee consisting of the core leaders and the PI, who will be the interface with HIRN and NIDDK leadership. HPAP-T2D will provide physiologic, genomic, genetic, and histological analysis of the pancreas in type 2 diabetes at unprecedented detail, share the rich data with researchers world-wide before publication, and thus enable breakthrough discoveries in our understanding of this disease that has reached epidemic levels world-wide.

Penn Human Pancreas分析计划 - T2D 抽象的 建立在我们现有的基础设施和科学合作的基础上，并获得了专业知识 在1型糖尿病的HPAP工作的头两年中，我们组装了五个核心 从胰腺采购和胰岛隔离到数据集成，专业知识不等。这些 核心构成了宾夕法尼亚州人类胰腺分析计划的核心A - T2D完全基于宾夕法尼亚大学。核心A将获得人类的范围 胰腺和详细的供体病史；下一个执行高分辨率HLA打字 生成测序；分离胰岛；并将胰岛和组织分配到其他核心以进一步 分析或处理。核心B将对孤立的胰岛进行物理表型。核 C将对孤立岛的分子分析进行多种高级方式，包括 分类胰岛细胞种群的RNASEQ，ATACSEQ和DNA甲基分析；单细胞 atacseq和rnaseq，以及用于20个以上细胞的单细胞定量的质量细胞仪 表面和细胞内标记。核心D将使用多种方式处理组织 允许使用高级技术（例如多重免疫染色）进行分析， 整个幻灯片成像和成像质量细胞术。该核心还将存档组织，DNA和 血液以及其他T2D相关的器官，例如骨骼肌，肠，脂肪组织 和肝脏，供其他NIDDK批准的宪法使用。最后，核心E将组装， 注释并维护该程序及其成员研究者的开放访问数据库 并与HIRN合作，共享两个程序的数据。整个程序将 由由核心领导人和PI组成的执行委员会指导的 与HIRN和NIDDK领导力的接触。 HPAP-T2D将提供生理，基因组，遗传， 以及对2型糖尿病中胰腺的组织学分析，以前所未有的细节共享 发表前全球研究人员的丰富数据，因此可以实现突破 在我们对这种疾病的理解中发现，在全球范围内已达到流行病。