Female Reproductive Tissue Mapping Center

女性生殖组织测绘中心

基本信息

批准号：
10268239
负责人：
LOUISE CHANG LAURENT
金额：
$ 60万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
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：
2020-09-25 至 2022-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10268239
关键词：
3-Dimensional ATAC-seq Adoption Antibodies Architecture Atlases Benign Biology Biomechanics Cell Communication Cell Proliferation Cells Clinical Clinical Data Clinical Research Collaborations Collection Communication Communities Computational Biology Cytometry Data Data Analyses Data Set Discipline of obstetrics Disease Distant Endometrial Endometrium Endothelial Cells Endothelium Ensure Evaluation Extracellular Matrix Female Female infertility Freezing Functional disorder Future Generations Goals Growth Gynecologic Pathology Gynecologic Surgical Procedures Gynecology Histologic Histology Human BioMolecular Atlas Program Human Resources Image In Situ Inflammation Infrastructure Kidney Lead Life Longevity Luteal Phase Lymphatic System Magnetic Resonance Imaging Malignant Female Reproductive System Neoplasm Mammalian Oviducts Maps Menopause Menstrual cycle Menstruation Metadata Microscopic Modality Molecular Molecular Profiling Myometrial Normal Range Normal tissue morphology Nucleic Acids Nursing Faculty Operative Surgical Procedures Organ Outcome Ovary Pathology Perfusion Perinatal Periodicity Physiological Placenta Placenta Accreta Population Postmenopause Pre-Eclampsia Pregnancy Pregnancy Outcome Pregnant Women Premenopause Process Property Proteomics Puberty Public Health Quality Control Radiology Specialty Research Research Infrastructure Research Personnel Resolution Resource Sharing Resources Sampling Signal Transduction Structure Technology Testing Tissues Translational Research Ultrasonography Uterus Visualization Woman calcification cell type cohort collaboratory data harmonization data management data sharing data standards endometriosis experience female reproductive system human data human female in vivo in vivo imaging interoperability metadata standards mimicry multiple omics multiscale data new technology novel pathology imaging pregnant preservation programs recruit reproductive reproductive organ single-cell RNA sequencing targeted treatment technology development therapy development tool transcriptomics trophoblast

项目摘要

SUMMARY The placenta, uterus, ovary, and fallopian tube act in concert to achieve successful pregnancy outcomes. These organs undergo marked changes in structure and function throughout the lifespan, coordinating with one another via direct and distant cell-cell interactions. Here, we propose to generate and integrate data from in vivo imaging and ex vivo histopathologic, biomechanical, and multi-omic spatial profiling data, in order to generate reference multiscale 3D maps of healthy human female reproductive organs representing a range of normal physiologic states that exist at different points in a woman’s life. These will serve as key frames of reference for future studies aiming to discover how perturbation of tissue structure and function leads to organ dysfunction and disease. Our team is well-equipped to achieve this goal, with expertise in clinical Obstetrics & Gynecology and Placental/Perinatal and Gynecologic Pathology, imaging, spatial molecular profiling, single- cell omics, extracellular matrix (ECM) biology, biomechanical testing, data management, and computational biology. We will leverage our well-established translational research infrastructure to recruit diverse cohorts of healthy pregnant women and non-pregnant premenopausal and postmenopausal women undergoing gynecologic surgery for benign indications. We will then perform in vivo imaging using MRI and ultrasound to delineate tissue structure, perfusion, inflammation, calcifications, and other features. After delivery/surgery, tissues will be rapidly sampled, processed, and stored in multiple ways (fresh, flash frozen, preserved in solutions for optimal nucleic acid analysis, and FFPE) to enable generation of high-quality data using a variety of molecular approaches, with extra samples retained for future studies. Detailed review of clinical data and formal histopathologic evaluation of adjacent tissue sections will be performed to confirm that normal tissue has been obtained from subjects with normal outcomes. Initial ex vivo analysis will include biomechanical testing, extracellular matrix proteomics, and bulk and single-cell RNAseq and ATACseq. The results of these studies will be analyzed to identify targets for the subsequent imaging mass cytometry (IMC) and spatial transcriptomic studies. These data types will be integrated to enable mapping of the relationships among different cell types and between cells and the surrounding extracellular matrix on the microscopic level, and between tissue architecture and the biomechanical properties and imaging features on a macroscopic level. The unique populations of endothelial cells in the placenta and the endothelial mimicry of the extravillous trophoblast will provide unique opportunities to integrate with other endothelial-centric HuBMAP projects (e.g. lymphatic system, endothelial atlas, and kidney atlas). Close interactions with other HuBMAP Centers will be established to enable harmonization of data and metadata standards, sharing of resources (e.g. antibodies with HuBMAP Centers that are developing/using CODEX and MIBI-TOF), rapid adoption of new technologies, collaborative data analysis, and rapid sharing of data with the HIVE and the broader scientific community.

概括 lopeta，子宫，卵巢和输卵管协同作用，以实现成功的妊娠结局。这些器官在整个寿命中都经历了结构和功能的明显变化，与通过直接和遥远的细胞 - 细胞相互作用彼此。在这里，我们建议生成和集成数据体内成像和离体组织病理学，生物力学和多摩尼克空间分析数据，以便为了生成健康的人类女性复制器官的参考多尺度3D图，代表一系列正常的生理状态存在于女人一生中不同地点。这些将作为关键框架参考未来研究的参考，旨在发现组织结构和功能的扰动如何组织功能障碍和疾病。我们的团队有足够的能力实现这一目标，并具有临床产科专业知识和妇科，胎盘/围产期和妇科病理学，成像，空间分子分析，单个细胞磁体，细胞外基质（ECM）生物学，生物力学测试，数据管理和计算生物学。我们将利用我们成熟的翻译研究基础设施来招募潜水员队列健康的孕妇和非妊娠前期和绝经后妇女正在接受妇科手术的良性适应症。然后，我们将使用MRI和超声检查进行体内成像描绘组织结构，灌注，注射，计算和其他特征。分娩/手术后，组织将通过多种方式迅速采样，处理和存储（新鲜，闪光冷冻，保存在最佳核酸分析的解决方案，以及FFPE），可以使用一种品种生成高质量数据分子方法，保留了额外的样品以供将来的研究。详细审查临床数据和将进行相邻组织切片的形式组织病理学评估，以确认正常组织已经从具有正常结果的受试者获得。初始的离体分析将包括生物力学测试，细胞外基质蛋白质组学以及大量和单细胞RNASEQ和ATACSEQ。这些结果将分析研究以识别随后成像质量细胞仪（IMC）和空间的目标转录组研究。这些数据类型将集成以启用关系映射不同的细胞类型以及细胞和周围细胞外基质之间的微观水平，以及在宏观水平上组织结构与生物力学特性和成像特征之间。斑点中的内皮细胞的独特种群和散发的内皮模仿滋养细胞将为与其他以内皮中心的Hubmap项目（例如，淋巴系统，内皮地图集和肾脏地图集）。与其他Hubmap中心的紧密互动将是建立以实现数据和元数据标准的协调，共享资源（例如抗体使用正在开发/使用Codex和Mibi-Tof的Hubmap中心，快速采用新技术，协作数据分析，并与Hive和更广泛的科学界快速共享数据。