Female Reproductive Tissue Mapping Center

女性生殖组织测绘中心

• 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
• 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

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.

总结 胎盘、子宫、卵巢和输卵管协同作用以实现成功的妊娠结局。 这些器官在整个生命周期中经历结构和功能的显著变化， 通过直接和远距离的细胞与细胞相互作用相互作用。在这里，我们建议从以下方面生成和整合数据： 体内成像和离体组织病理学、生物力学和多组学空间分布数据，以便 生成健康人类女性生殖器官的参考多尺度3D图，其表示一系列 女性生命中不同阶段的正常生理状态。这些将作为关键框架， 为未来的研究提供参考，旨在发现组织结构和功能的扰动如何导致器官 功能障碍和疾病。我们的团队拥有完善的设备来实现这一目标，拥有临床产科和 妇科和胎盘/围产期和妇科病理学，成像，空间分子谱，单- 细胞组学、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完善的转化研究基础设施，招募不同的群体， 健康孕妇和未怀孕的绝经前和绝经后妇女， 良性适应症的妇科手术。然后，我们将使用MRI和超声进行体内成像， 描绘组织结构、灌注、炎症、钙化和其他特征。分娩/手术后， 组织将以多种方式（新鲜、快速冷冻、保存在 用于最佳核酸分析的解决方案和FFPE），以使用各种 分子方法，保留额外的样本用于未来的研究。详细审查临床数据， 将对相邻组织切片进行正式的组织病理学评价，以确认正常组织 从正常结果的受试者中获得。初始离体分析将包括生物力学 测试，细胞外基质蛋白质组学，以及批量和单细胞RNAseq和ATACseq。的结果予以 研究将进行分析，以确定后续成像质量细胞术（IMC）和空间的目标 转录组学研究。这些数据类型将被集成，以便能够映射 不同的细胞类型和细胞与周围细胞外基质之间的微观水平，和 组织结构和生物力学特性以及宏观层面上的成像特征之间的关系。 胎盘中独特的内皮细胞群和绒毛外膜的内皮拟态 滋养层将提供独特的机会，与其他内皮中心HuBMAP项目（例如， 淋巴系统、内皮图谱和肾图谱）。将与其他HuBMAP中心密切互动， 建立数据和元数据标准的统一，资源共享（如抗体 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，以及与HIVE和更广泛的科学界快速共享数据。