Penn TMC: Organ-Specific Project

Penn TMC：特定器官项目

• 批准号: 10117839
• 负责人: Kurt T Barnhart
• 金额: $ 47.58万
• 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/10117839
• 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 environment; 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、输卵管和卵巢组成 任何成人器官系统的结构和功能的一些最动态的变化 每月和整个生命周期中的组织组织对于女性生殖系统至关重要。 因为它负责协调的循环变化，这不仅是繁殖所必需的，而且也是 在这里，我们建议将我们独特的途径结合起来。 凭借我们在单细胞生物学方面的专业知识，建立了完整的正常女性生殖系统 我们将收集和管理受试者/捐赠者的女性生殖系统比例分子图。 样本来生成多尺度分子图：我们将利用我们的受试者/捐赠者群体来 对同一受试者（16 个供体）的多达 22 个组织位置进行全面采样，以及样本 总的来说，我们建议通过大量捐赠者的单个组织来收集时间信息。 使用多重检测从四个女性生殖器官的 22 个位置收集约 700 个组织样本 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 种不同方案）、多重 FISH (clampFISH)、原位开放染色质以及同步 与其他 TMC 合作进行总共 6 项 RNA/开放染色质测定和蛋白质测定 我们还将使用不同的分析方法开发女性生殖系统的 3D 数字模型。 受试者/捐赠者成像数据，并开发相关的空间注释工具来索引我们的临床样本 SA1 中的集合以及解剖坐标所有分析数据都将注册到我们的 3D 解剖图上。 将与 HIVE 通用坐标框架集成。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、策划和 我们将使用经过充分验证的协议（例如 10X Chromium 平台）或 我们将与您合作，在将分子检测转移到生产管道之前对其进行验证和优化。 其他 TMC 以及其他 HuBMAP 团体制定社区标准和验证方法 对于分子分析，我们将构建一个系统化的数据收集和生产流程。 简化从临床采样到 3D 模型索引、分子测定、数据分析的流程 我们的数据收集活动的完成将创造前所未有的公众。 资源将增强我们对人类生殖生物学的理解并影响妇女的健康。