Penn TMC: Organ-Specific Project

Penn TMC：特定器官项目

• 批准号: 10461164
• 负责人: Kurt T Barnhart
• 金额: $ 92.42万
• 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/10461164
• 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--包括子宫、输卵管和卵巢--经历了 成人人体器官系统在结构和功能上的一些最动态的变化 每月一次，终生一次。女性生殖系统中的组织组织是至关重要的 因为它负责协调的循环变化，不仅是繁殖所必需的，也是 维护多个其他器官系统。在这里，我们建议将我们独特的访问 整个正常的女性生殖系统用我们在单细胞生物学方面的专业知识建立了多个 女性生殖系统的比例尺分子图。我们将收集和管理受试者/捐赠者 生成多尺度分子图谱的样本：我们将利用我们的受试者/捐赠者群体来 从同一受试者(16名捐赠者)身上采集多达22个组织部位的综合样本，以及样本 通过单个组织对大量捐赠者收集时间信息。总括而言，我们建议 用多次化验从四个女性生殖器官收集22个地点的~700个组织样本 医疗模式。我们将生成空间协调的多尺度分子图：我们将收集scRNAseq (3种不同方案)、多重FISH(夹层FISH)、原位开放染色质以及同步 与其他TMC合作进行的RNA/开放染色质分析和蛋白质分析，共六个 不同的检测方法。我们还将开发女性生殖系统的3D数字模型，使用 受试者/供体成像数据，并开发相关的空间注释工具来索引我们的临床样本 SA1中包含解剖坐标的集合。所有化验数据都将注册到我们的3D解剖图中 这将与蜂窝共同坐标框架相结合。来自主题记录的所有元数据， 临床程序、分子程序和信息学管道将被收集、管理和 作为结构化数据存储。我们将使用经过充分验证的协议(例如，10X Chromium平台)或 在将分子分析转移到生产管道之前，验证和优化分子分析。我们将与 其他TMC以及其他HuBMAP小组制定社区标准和验证方法 用于分子分析。对于系统的数据收集和生产流水线工作，我们将建设一个 简化了从临床采样、3D模型索引、分子分析到数据分析的流程 和协调性。我们数据收集活动的完成将创造一个前所未有的公众 这将加强我们对人类生殖生物学的了解，并影响妇女的健康。