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 任何成人器官系统的结构和功能的一些最动态的变化， 每月一次，终生。女性生殖系统中的组织结构至关重要 因为它负责协调的周期性变化，这不仅是繁殖所必需的， 维持多个其他器官系统。在这里，我们建议将我们独特的访问权限与 利用我们在单细胞生物学方面的专业知识， 女性生殖系统的分子图。我们将收集和管理受试者/供体 样本生成多尺度分子图谱：我们将利用我们的受试者/供体人群， 从同一受试者（16名供体）全面采集多达22个组织位置，以及样本 一个单一的组织在大量的捐助者收集时间信息。总的来说，我们建议 使用多项检测从4个雌性生殖器官的22个位置采集约700份组织样本 方式。我们将生成空间协调的多尺度分子图谱：我们将收集scRNAseq （3种不同的方案），多重FISH（clampFISH），原位开放染色质，以及同时 RNA/开放染色质分析和蛋白质分析，与其他TMC合作，共进行6次 不同的分析方法。我们还将开发女性生殖系统的3D数字模型， 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 在SA 1中收集解剖坐标。所有分析数据将配准到我们的3D解剖图 这将与HIVE共同协调框架相结合。所有目标记录的元数据， 临床程序，分子程序和信息学管道将被收集，策划， 存储为结构化数据。我们将使用经过充分验证的协议（例如，10 X Chromium平台）或 在将分子分析转移到生产管道之前验证和优化它们。我们将与 其他TMCs以及其他HuBMAP小组制定社区标准和验证方法 用于分子检测为了进行系统的数据收集和生产管道工作，我们将建立一个 从临床采样到3D模型索引、到分子测定、到数据分析的简化流程 和协调我们的数据收集活动的完成将创造一个前所未有的公众 这将提高我们对人类生殖生物学的理解，并影响妇女的健康。