The Human Pancreas Analysis Program for Type 2 Diabetes

2 型糖尿病人类胰腺分析项目

基本信息

批准号：
10568985
负责人：
KLAUS H KAESTNER
金额：
$ 300万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
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/10568985
关键词：
ATAC-seq Adipose tissue Adolescent Architecture Bioenergetics Biological Assay Biology Biopsy Blood Calcium Cell physiology Cell surface Cells Collaborations Colon Communities Cyclic GMP Cytometry DNA Data Data Analyses 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 Sorting Stains Technology Tissues United States National Institutes of Health Universities Visualization Work biobank data access data integration data resource data sharing data submission data visualization epigenomics experience human leukocyte antigen testing human tissue improved islet maturity onset diabetes of the young member methylome migration molecular phenotype morphometry multidimensional data next generation sequencing programs protein biomarkers quantitative imaging response sample fixation single-cell RNA sequencing tissue archive transcriptome transcriptome sequencing whole slide imaging

项目摘要

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.

宾夕法尼亚大学人类胰腺分析项目 – T2D 抽象的建立在我们现有的基础设施和科学合作以及所获得的专业知识的基础上在针对 1 型糖尿病的 HPAP 努力的头两年中，我们组装了五个核心拥有从胰腺采购、胰岛分离到数据集成的专业知识。核心构成了全面综合的宾夕法尼亚大学人类胰腺分析计划 – T2D 完全位于宾夕法尼亚大学，Core A 将采购一系列人类。接下来执行高分辨率 HLA 分型世代测序；分离胰岛；并将胰岛和组织分配到其他核心以进行进一步的研究 Core B 将对分离的胰岛进行生理表型分析。 C 将执行多种先进模式对孤立胰岛进行分子分析，包括分选的胰岛细胞群的 RNAseq、ATACseq 和 DNA 甲基化组分析； ATACseq 和 RNAseq，以及用于 20 多个细胞的单细胞定量的质谱流式细胞术 Core D 将使用多种方式处理组织。允许使用先进技术进行分析，例如多重免疫荧光染色，全玻片成像和质谱流式细胞仪成像该核心还将存档组织、DNA 和血液以及其他 T2D 相关器官，如骨骼肌、肠道、脂肪组织最后，Core E 将组装起来，供其他 NIDDK 批准的联盟将来使用。为该计划及其成员研究人员注释和维护一个开放访问数据库，并与 HIRN 合作共享两个项目的数据。由核心领导和 PI 组成的执行委员会领导，PI 是与 HIRN 和 NIDDK 领导层的接口将提供生理、基因组、遗传、以前所未有的细节对 2 型糖尿病患者的胰腺进行组织学分析，分享在发表之前与世界各地的研究人员收集丰富的数据，从而实现突破我们对这种在世界范围内已达到流行水平的疾病的认识有了新的发现。