The Human Pancreas Analysis Program for Type 2 Diabetes

Penn人类胰腺分析程序-T2 D 摘要 基于我们现有的基础设施和科学合作，以及获得的专业知识， 在针对1型糖尿病的HPAP工作的前两年，我们已经收集了五个核心 从胰腺获取和胰岛分离到数据整合。这些 核心形成一个全面和综合的宾夕法尼亚大学人类胰腺分析计划- T2 D完全基于宾夕法尼亚大学。核心A将获得一系列人类 胰腺和详细的供体病史;在下一次手术前进行高分辨率HLA分型 第二代测序;分离胰岛;并将胰岛和组织分配给其他核心， 分析或处理。核心B将对分离的胰岛进行生理表型分析。核心 C将进行多种先进的模式，分离胰岛的分子概况，包括 分选的胰岛细胞群的RNAseq、ATACseq和DNA甲基化组分析;单细胞 ATACseq和RNAseq以及用于20个以上细胞的单细胞定量的质谱细胞术 表面和细胞内标记物。核心D将使用多种方式处理组织， 允许使用先进技术如多重免疫荧光染色进行分析， 全载玻片成像和成像质谱细胞计数。这个核心还将保存组织、DNA和 血液以及其他T2 D相关器官，如骨骼肌、肠、脂肪组织 和肝脏供其他NIDDK批准的财团将来使用。最后，核心E将组装， 注释和维护一个开放获取的数据库，供该计划及其成员研究人员使用， 并与HIRN合作，共享来自两个项目的数据。整个计划将 由核心领导人和PI组成的执行委员会领导，PI将是 与HIRN和NIDDK领导层进行沟通。HPAP-T2 D将提供生理，基因组，遗传， 2型糖尿病的胰腺组织学分析在前所未有的细节，分享 在出版前与世界各地的研究人员进行丰富的数据交流，从而实现突破 我们对这种疾病的了解已经达到了世界范围的流行程度。

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.