The Human Pancreas Analysis Program for Type 2 Diabetes

宾夕法尼亚大学人类胰腺分析程序-T2D 摘要 建立在我们现有的基础设施和科学合作以及获得的专业知识基础上 在HPAP治疗1型糖尿病的头两年里，我们组装了五个核心 拥有从胰腺采购和胰岛隔离到数据集成的专业知识。这些 核心构成了宾夕法尼亚大学全面和综合的人类胰腺分析计划- T2D完全基于宾夕法尼亚大学。核心A将获得一系列人类 胰腺和详细的捐赠者病史；在NEXT之前进行高分辨率的HLA配型 世代测序；分离胰岛；并将胰岛和组织分布到其他岩心以进一步 分析或处理。核心B将对孤立的胰岛进行生理表型鉴定。堆芯 C将对孤立的胰岛进行多种先进的分子图谱分析，包括 分选胰岛细胞群体的RNAseq、ATACseq和DNA甲基组分析；单细胞 ATACseq和RNAseq，以及用于20多个细胞的单细胞定量的质量细胞术 表面和细胞内标记物。核心D将使用多种模式处理组织，这将 允许使用先进的技术进行分析，如多重免疫荧光染色， 全玻片成像和成像质量细胞术。这个核心还将存档组织、DNA和 血液以及其他与T2D相关的器官，如骨骼肌、肠道、脂肪组织 和肝脏，供其他NIDDK批准的财团未来使用。最后，核心E将组装， 为本计划及其成员--研究人员注释和维护一个开放获取的数据库， 并与HIRN合作共享来自这两个计划的数据。整个项目将 由执行委员会领导，执行委员会由核心领导人和私人投资委员会组成，他们将是 与Hirn和NIDDK领导层沟通。HPAP-T2D将提供生理、基因组、遗传、 并对2型糖尿病患者的胰腺进行了前所未有的详细组织学分析，分享 在发表前与世界各地的研究人员一起提供丰富的数据，从而实现突破 在我们对这种已经在世界范围内流行的疾病的理解上的发现。

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.