The Bone Marrow Multi-modal Imaging Core

骨髓多模态成像核心

• 批准号: 10531007
• 负责人: Sean Curtis Bendall
• 金额: $ 103.56万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10531007
• 关键词: Acids; Age; Aging; Algorithms; Anatomy; Androgens; Antibodies; Architecture; Archives; Atlases; Automobile Driving; Autopsy; Biological Assay; Blood; Blood Cells; Bone Marrow; Bone Marrow Cells; Caliber; Carbohydrates; Cell Communication; Cell Maturation; Cell Therapy; Cells; Clinical; Collection; Communicable Diseases; Complement; DNA Damage; Data; Dependence; Development; Diagnosis; Diagnostic; Disease; Edetic Acid; Engineering; Ensure; Extracellular Matrix Proteins; Formalin; Future; Gender; Gene Expression Profile; Genetic Transcription; Goals; Head; Hematopathology; Hematopoiesis; Hematopoietic; Hematopoietic stem cells; Hemostatic function; Histologic; Homeostasis; Hospitals; Human; Human BioMolecular Atlas Program; Image; Imaging technology; Immune; Immunophenotyping; Investigation; Maps; Marrow; Mass Spectrum Analysis; Metabolism; Methods; Molecular; Molecular Profiling; Molecular Target; Morphology; Multimodal Imaging; Multiple Anatomic Sites; Multiplexed Ion Beam Imaging; Neighborhoods; Nucleic Acids; Organ; Organ Procurements; Oxygen; Pathologist; Pathology; Patients; Pattern; Polysaccharides; Population; Post-Translational Protein Processing; Process; Proteins; Protocols documentation; RNA; Race; Research; Resolution; Resources; Retrospective Studies; Sampling; Sex Differences; Site; Spatial Distribution; Specimen; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Sternum; Stromal Cells; Structure; Tissue Banks; Tissue imaging; Tissues; Universities; Variant; adaptive immunity; age effect; age related; antimicrobial; base; bone quality; cohort; data integration; demographics; hip replacement arthroplasty; hormonal signals; image processing; insight; mass spectrometric imaging; multimodal data; multimodality; multiplexed imaging; nano-string; nanoscale; preservation; programs; prospective; rib bone structure; skeletal; spine bone structure; stem cells; tissue archive; transcriptome; transcriptomics

Project Summary - Organ Specific Project Bone marrow produces blood cells whose functions range from oxygen delivery to anti-microbial defense to hemostasis, all originating from hematopoietic stem cells (HSC). To sustain and regulate this branched maturation process, bone marrow stromal cells form multiple niche microenvironments, each tailored to the needs of a particular developing blood cell population. The Organ Specific Project (OSP) aims to systematically and quantitatively dissect the cellular composition and spatial organization of human bone marrow microenvironments using highly-multiplexed imaging technologies. The resulting detailed maps will serve as an open and global platform for understanding which cells and interactions are critical for each branch of hematopoietic maturation. Complementing prior HuBMAP projects, this OSP will compare patient-matched bone marrow from multiple anatomical sites and examine effects of age, gender, and race. Samples will be collected by three different strategies, each with a different investigational focus: (1) prospective collection of marrow from 6 deceased donors at vertebra, rib, and sternum to examine differences between the 3 anatomical sites, (2) prospective collection from 16 hip arthroplasty femoral head specimens for differences between age ranges, (3) 80 diagnostically normal iliac crest bone marrow samples from the Stanford Pathology archive for differences between races and genders. Once collected, we will process samples through existing clinically-validated pre- analytical processing pipelines to maximize compatibility with current and future assays. We will define cellular identities and cell states at the transcriptional, translational, and post-translational levels using Nanostring DSP, Multiplexed Ion Beam Imaging (MIBI), and MALDI-MSI, which generate quantitative spatial maps of RNA, protein, and N-glycans, respectively. Our study team includes the inventors of MIBI, a pioneer in MALDI-MSI, inventors of tissue image processing algorithms, experts in human HSCs and hematopoiesis, and a practicing hematopathologist who routinely diagnoses human bone marrow. Integrating these data together, we will quantitatively and systematically identify bone marrow niche microenvironments by their patterns of cellular composition and architectural organization. Comparing microarchitectures across our three cohorts will elucidate the effects of anatomical site, age, race, and gender. Understanding which hematopoietic and stromal cells are lost through age, in what order, at which sites, and within which microenvironments will provide insight into human aging and its relationship to metabolism and DNA damage. Differences between sexes likely reveal the influence of androgen and hormone signaling. Variations between races may reflect evolutionary forces such as infectious diseases. These insights can then be leveraged to diagnose and dissect disease states and engineer new cellular therapies.

项目摘要 - 器官特定项目 骨髓会产生血细胞，其功能从氧递送到抗微生物防御到 止血，均起源于造血干细胞（HSC）。维持和规范这一分支 成熟过程，骨髓基质细胞形成多个利基微环境，每个环境都定制 特定发展的血细胞种群的需求。器官特定项目（OSP）旨在系统地 并定量剖析人骨髓的细胞组成和空间组织 使用高度多形成像技术的微环境。由此产生的详细地图将作为 开放和全球平台，以了解哪些细胞和相互作用对于每个分支至关重要 造血成熟。 补充先前的Hubmap项目，该OSP将比较多个患者匹配的骨髓 解剖场所并检查年龄，性别和种族的影响。样品将通过三种不同 策略，每个策略都有不同的研究重点：（1）从6名死者那里收集骨髓 椎骨，肋骨和胸骨的供体检查3个解剖位点之间的差异，（2）前瞻性 从16个髋关节置换术股头样本收集的年龄范围之间差异的收集，（3）80 来自斯坦福病理学的诊断正常的iliac峰骨髓样品归档 在种族和性别之间。一旦收集，我们将通过现有的临床验证预验证处理样品 分析处理管道，以最大程度地与当前和未来测定法相兼容。 我们将在转录，翻译和翻译后定义细胞身份和细胞状态 使用纳米串DSP，多路复用离子束成像（MIBI）和MALDI-MSI的水平，它们产生 RNA，蛋白质和N-聚糖的定量空间图。我们的学习团队包括 Mibi，Maldi-MSI的先驱，组织图像处理算法的发明者，人类HSC的专家和 造血和练习血小病学家常规诊断人骨髓。整合 这些数据一起，我们将通过定量和系统地识别骨髓利基微环境 他们的细胞组成和建筑组织模式。 比较我们三个队列中的微构造将阐明解剖部位，年龄，种族， 和性别。了解哪种造血细胞和基质细胞在年龄中丢失了，以什么顺序 微环境将提供对人类衰老及其与其与之的关系的遗址 代谢和DNA损伤。性别之间的差异可能揭示了雄激素和激素的影响 信号。种族之间的变化可能反映了进化力，例如传染病。这些见解 然后可以利用以诊断和剖析疾病状态和工程师新的细胞疗法。