Female Reproductive Tissue Mapping Center

女性生殖组织测绘中心

• 批准号: 10119154
• 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/10119154
• 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; endometriosis; experience; female reproductive system; human data; human female; in vivo; in vivo imaging; interoperability; 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.

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