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 骨髓产生血细胞，其功能范围从氧气输送到抗微生物防御 止血，全部源自造血干细胞（HSC）。为了维持和规范这个分支 在成熟过程中，骨髓基质细胞形成多个生态位微环境，每个微环境都针对 特定发育中的血细胞群的需要。器官特定项目 (OSP) 旨在系统地 定量剖析人体骨髓的细胞组成和空间组织 使用高度多重成像技术的微环境。由此产生的详细地图将作为 开放的全球平台，用于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。 作为对之前 HuBMAP 项目的补充，该 OSP 将比较来自多个患者的匹配骨髓 解剖部位并检查年龄、性别和种族的影响。样本将由三个不同的机构收集 策略，每种策略都有不同的研究重点：(1) 前瞻性收集 6 名死者的骨髓 椎骨、肋骨和胸骨的捐赠者检查 3 个解剖部位之间的差异，(2) 前瞻性 收集 16 个髋关节置换股骨头标本以了解年龄范围之间的差异，(3) 80 来自斯坦福病理学档案馆的诊断正常髂嵴骨髓样本，以找出差异 种族和性别之间。一旦收集完毕，我们将通过现有的临床验证预处理样本 分析处理流程，以最大限度地提高与当前和未来检测的兼容性。 我们将定义转录、翻译和翻译后的细胞身份和细胞状态 使用 Nanostring DSP、多路复用离子束成像 (MIBI) 和 MALDI-MSI 进行级别处理，生成 分别绘制 RNA、蛋白质和 N-聚糖的定量空间图。我们的研究团队包括以下发明人 MIBI，MALDI-MSI 的先驱，组织图像处理算法的发明者，人类 HSC 和 造血功能，以及一位经常诊断人类骨髓的执业血液病理学家。整合 将这些数据结合起来，我们将通过以下方式定量和系统地识别骨髓生态位微环境： 他们的细胞组成和建筑组织的模式。 比较我们三个队列的微结构将阐明解剖部位、年龄、种族、 和性别。了解哪些造血细胞和基质细胞随着年龄的增长而丢失，以什么顺序、以什么时间丢失 地点，以及其中的微环境将提供对人类衰老及其关系的深入了解 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 发信号。种族之间的差异可能反映了诸如传染病等进化力量。这些见解 然后可以用来诊断和剖析疾病状态并设计新的细胞疗法。