Center for Developmental Mapping of Heart and Bone Tissues

心脏和骨组织发育图谱中心

基本信息

批准号：
10251350
负责人：
KATHRIN M BERNT
金额：
$ 50万
依托单位：
CHILDREN'S HOSP OF PHILADELPHIA
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-01 至 2022-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10251350
关键词：
Adult Age Aging Algorithms Anatomy Atlases Automobile Driving Awareness Basic Science Biological Assay Biology Biomedical Research Bone Diseases Bone Tissue Boston Cell Communication Cell Nucleus Cells Cellular Assay Cellular Structures Chromatin Clinical Data Clinical Research Collaborations Communication Communities Complex Computational algorithm Computer Models Computer software Computing Methodologies Data Databases Detection Development Diagnosis Disease Emerging Technologies Ethnic Origin Fluorescent in Situ Hybridization Follow-Up Studies Freezing Genetic Transcription Health Heart Heart Diseases Hematological Disease Heterogeneity Human Human BioMolecular Atlas Program Image Imaging technology Informed Consent Infrastructure Iowa Joints Knowledge Longevity Maps Mediating Medical Methods Molecular Molecular Profiling Normalcy Organ Outcome Pathogenesis Pattern Pediatric Hospitals Pennsylvania Phenotype Philadelphia Physiological Play Population Prognosis Proteins Protocols documentation RNA Regulatory Pathway Research Research Personnel Role Signal Pathway Signal Transduction Pathway Small Nuclear RNA Spatial Distribution Specimen Techniques Technology Tissue Donors Tissue Preservation Tissue Procurements Tissues Translational Research Transposase Universities Visualization base biobank bone bone quality burden of illness cell type cellular imaging complex data computational pipelines computerized tools data sharing epidemiologic data genomic data human disease human tissue improved indexing infancy insight molecular imaging multiple omics multiplexed imaging novel open source precision medicine searchable database sex single cell analysis transcriptome sequencing user-friendly

项目摘要

PROJECT SUMMARY - OVERALL Both human bone and heart present remarkable anatomical, cellular and functional heterogeneity, with specialized cellular structures performing distinct yet essential physiological functions. A significant gap of knowledge is that different cells' molecular signature, spatial distribution and interactions, and functional state remain little understood for both organs. Although spatially separated, growing evidence suggests that a bone- heart communication axis plays a critical role in normal development and pathogenesis of these two organs and possibly other organs. Joint analysis of the two organs could reveal novel insights into the microenvironment organization and signaling pathways underlying the inter-organ communication. We therefore propose the in-depth characterization of these two organs which, together, account for a large fraction of human disease burden. We will map molecular and cellular changes in the tissue over the course of human lifespan using comprehensive multi-dimensional single-cell and imaging technologies. The final product will impact research of these two organs in the following manner: 1) Organ Atlases: spatially resolved atlases will provide a highly user friendly, publicly available, searchable database of the most comprehensive multi- omic, single cell analysis of the two organs. Molecular data will be richly annotated with additional clinical and epidemiological data. 2) Computational methods: in addition to the data, the critical computational tools and pipelines developed in this project will be available to the research community. These include methods and pipelines for processing multi-omics and imaging data, inference of cell-specific regulatory and signaling pathways, correlation of mesoscale imaging and molecular imaging features, as well as database algorithms for the query, exploration and visualization of highly complex data. 3) Access to biospecimens for follow-up studies: biospecimens collected in this project will be banked and made available to the biomedical research community. These include freshly frozen and fixed specimens and tissue sections. In summary, the proposed project will broadly impact the entire research community and jumpstart basic-science and medical discoveries based on a sophisticated understanding of the key molecular circuits underlying the development and aging of these two organs.

项目摘要 - 总体人骨和心脏都表现出显着的解剖，细胞和功能异质性，具有专门的细胞结构具有不同的生理功能。一个很大的差距知识是不同细胞的分子特征，空间分布和相互作用以及功能状态对于两个器官，几乎没有理解。尽管在空间上分离，但越来越多的证据表明骨心脏通讯轴在这两个器官的正常发育和发病机理中起着关键作用还有其他器官。对两个器官的联合分析可以揭示对该机构的新见解微观环境组织和信号通路是组织间通信的基础。我们因此，提出了这两个器官的深入表征，共同考虑了一个大的人类疾病负担的一部分。我们将在整个过程中绘制组织中的分子和细胞变化人类使用全面的多维单电池和成像技术的寿命。最终产品将以以下方式影响这两个器官的研究：1）器官地图集：空间解析的地图集将提供一个高度用户友好的，公开可用的，可搜索的数据库两个器官的单细胞分析。分子数据将通过额外的临床和流行病学数据。 2）计算方法：除了数据，关键的计算工具和该项目中开发的管道将提供给研究社区。这些包括方法和用于处理多词和成像数据的管道，细胞特异性调节和信号的推断途径，中尺度成像和分子成像特征的相关性以及数据库算法对于查询，探索和可视化高度复杂的数据。 3）访问生物测量以进行随访研究：该项目中收集的生物测量将被库存并提供给生物医学研究社区。这些包括新鲜冷冻和固定的标本和组织切片。总而言之项目将广泛影响整个研究社区，并开始基本科学和医疗发现基于对开发和衰老基础的关键分子电路的复杂理解这两个器官。