Penn TMC: Organ-Specific Project

Penn TMC：特定器官项目

• 批准号: 10269929
• 负责人: Kurt T Barnhart
• 金额: $ 68.81万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-24 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10269929
• 关键词: 3-Dimensional; Adult; Anatomy; Atlases; Biological Assay; Cardiovascular Diseases; Cells; Cellular biology; Chromatin; Chromium; Clinical; Collaborations; Communities; Computer software; Data; Data Analyses; Data Collection; Deposition; Endocrine; Endocrine System Diseases; Endometrium; Ensure; Environment; Epigenetic Process; Female; Fertilization; Fetus; Generations; Geography; Germ Cells; Goals; Gonadal Steroid Hormones; Health; Home; Human; Human BioMolecular Atlas Program; Human body; Image; In Situ; Informatics; Life; Location; Longevity; Maintenance; Mammalian Oviducts; Maps; Medical Records; Metadata; Methods; Modality; Molecular; Oocytes; Organ; Ovary; Periodicity; Personal Satisfaction; Population; Procedures; Process; Production; Proteins; Protocols documentation; RNA; Records; Reproduction; Reproductive Biology; Resources; Sampling; Scheme; Stromal Cells; Structure; Time; Tissue Sample; Tissues; Uterus; Validation; Walking; Women' s Health; Work; annotation system; body system; cell community; data standards; digital models; embryo/fetus; female reproductive system; granulosa cell; implantation; indexing; molecular scale; mortality; natural Blastocyst Implantation; reproductive; reproductive organ; sample collection; structured data; theca cell; three-dimensional modeling

The female reproductive system—comprised of the uterus, fallopian tubes and the ovaries—undergoes some of the most dynamic changes in structure and function of any adult human organ system on a monthly basis and throughout life. Tissue organization in the female reproductive system is paramount as it is responsible for the coordinated cyclic changes necessary not only for reproduction but also for the maintenance of multiple other organ systems. Here, we propose to couple our unique access to the entire normal female reproductive system with our expertise in single cell biology to establish a multi- scale molecular map of the female reproductive system. We will collect and manage subject/donor samples to generate a multi-scale molecular map: We will leverage our subject/donor population to comprehensively sample up to 22 tissue locations from the same subject (16 donors), as well as sample a single tissue over a large number of donors to collect temporal information. In total, we propose to collect ~700 tissue samples over 22 locations from four female reproductive organs using multiple assay modalities. We will generate a spatially coordinated multi-scale molecular map: We will collect scRNAseq (3 different schemes), multiplex FISH (clampFISH), in situ open chromatin, as well as simultaneous RNA/open chromatin assays and protein assays in collaboration with other TMCs for a total of six different assay methods. We will also develop a 3D digital model of the female reproductive system using subject/donor imaging data, and develop associated spatial annotation tools to index our clinical sample collection in SA1 with anatomical coordinates. All assay data will be registered to our 3D anatomical map that will be integrated with the HIVE Common Coordinate Framework. All metadata from subject records, clinical procedures, molecular procedures, and informatics pipelines will be collected, curated, and deposited as structured data. We will use well-validated protocols (e.g., 10X Chromium platform) or validate and optimize molecular assays before moving them to production pipelines. We will work with other TMCs as well as other HuBMAP groups to develop community standards and validation methods for the molecular assays. For systematic data collection and production pipeline work, we will construct a streamlined process from Clinical Sampling, to 3D Model Indexing, to Molecular Assays, to Data Analysis and Coordination. The completion of our data collection activities will create an unprecedented public resource that will enhance our understanding of human reproductive biology and impact women’s health.

女性生殖系统（由子宫，输卵管和卵巢）构成 任何成人人体器官系统的结构和功能上最动态的变化 每月和一生。女性复制系统中的组织组织至关重要 因为它负责不仅需要复制的协调循环变化，而且还需要 维护多个其他器官系统。在这里，我们建议将我们独特地访问 整个正常的女性生殖系统，具有我们在单细胞生物学方面的专业知识，以建立多种 女性生殖系统的比例分子图。我们将收集和管理主题/捐助者 样品生成多尺度的分子图：我们将利用我们的受试者/供体人群 全面采样来自同一受试者（16个捐赠者）的22个组织位置以及样品 在大量捐赠者上进行的单个组织收集临时信息。我们总共建议 使用多个测定 方式。我们将生成一个空间协调的多尺度分子图：我们将收集scrnaseq （3种不同的方案），多重鱼（夹鱼），原位开放染色质以及同时 与其他TMC合作的RNA/开放染色质分析和蛋白质测定总共六个 不同的测定方法。我们还将使用使用女性生殖系统的3D数字模型 主题/供体成像数据，并开发了相关的空间注释工具来索引我们的临床样本 与解剖坐标的SA1收集。所有测定数据将注册到我们的3D解剖图 这将与Hive Comman Coordic框架集成。所有元数据来自主题记录， 临床程序，分子程序和信息管道将被收集，策划，并且 沉积为结构化数据。我们将使用经过良好验证的协议（例如10倍铬平台）或 在将其转移到生产管道之前，验证和优化分子测定。我们将与 其他TMC以及其他Hubmap组来开发社区标准和验证方法 对于系统的数据收集和生产管道工作，我们将构建一个 简化从临床抽样到3D模型索引，再到分子测定到数据分析的过程 和协调。我们的数据收集活动的完成将创建前所未有的公众 将增强我们对人类生殖生物学的理解并影响妇女健康的资源。