Multimodal histologic atlas of human bone marrow

人骨髓多模态组织学图谱

• 批准号: 10924351
• 负责人: Robert michael Angelo
• 金额: $ 5万
• 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 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10924351
• 关键词: Affect; Age; Aging; Anatomy; Antibodies; Archives; Atlases; Biological; Biological Assay; Blood Cells; Blood Group Antigens; Board Certification; Bone Marrow; Bone Marrow Cells; Bone structure; Cell Maturation; Cell Therapy; Cells; Clinical; Collection; Communities; Complement; DNA; Data; Data Analyses; Data Set; Diagnosis; Diameter; Doctor of Philosophy; Ensure; Erythroid; Future; Gender; Genetic Transcription; Goals; Hematopoiesis; Hematopoietic; Hematopoietic stem cells; Hemostatic function; Histologic; Human; Human BioMolecular Atlas Program; Image; Imaging technology; Length; Maps; Marrow; Metabolism; Modality; Morphology; Multiplexed Ion Beam Imaging; Neighborhoods; Nutritional; Oligonucleotides; Oxygen; Pathologist; Pathology; Patients; Phenotype; Physiologic calcification; Polysaccharides; Population; Process; Production; Proteins; Protocols documentation; Quality Control; RNA; Race; Reporter; Research Personnel; Sampling; Site; Skeleton; Source; Spatial Distribution; Specimen; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Standardization; Sternum; Stromal Cells; Structure; Technology; Tissue Banks; Tissue imaging; Tissues; Variant; Vision; Work; antimicrobial; arm; bone; cellular development; cohort; computerized tools; data analysis pipeline; data pipeline; demographics; ethnic diversity; femur head; glycosylation; hip replacement arthroplasty; human tissue; imaging modality; mass spectrometric imaging; meetings; multimodality; multiplexed imaging; multiscale data; nano-string; novel; preservation; progenitor; programs; prospective; quantitative imaging; rib bone structure; sample collection; spine bone structure; tissue mapping; tool; transcriptomics

Project Summary – Overall 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 process, bone marrow stromal cells form multiple niche microenvironments, each tailored to the needs of a particular developing blood cell population. Using highly-multiplexed imaging technologies, our proposed Bone Marrow Tissue Mapping Center (TMC) aims to systematically and quantitatively dissect the cellular composition and spatial organization of human bone marrow microenvironments. 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, and how these vary by anatomical site and across diverse patient demographics. The TMC 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 cross-disciplinary team not only includes the inventors of MIBI and a pioneer of MALDI-MSI, but also experts in human HSCs and human hematopoiesis and a practicing hematopathologist with expertise in histopathologic bone marrow diagnosis. To overcome the unique challenges of working with hard, mineralized bone, we will leverage parallel, robust, clinically-validated bone marrow processing pipelines which maximize and standardize sample quality and compatibility with current and future technologies. Integrating seamlessly into standard clinical workflows, our pipelines enable convenient sharing of prospectively-collected materials with the Tissue Core. Samples will be collected from three different sources: (1) prospective, patient-matched multi-site collection from deceased donors to examine differences between anatomical sites, (2) prospective collection of femoral head from hip arthroplasty specimens for differences between age ranges, (3) iliac crest bone in the Stanford Pathology archive for differences between races and genders. These multiple collection strategies, multiple sites, and different investigational focuses complement prior HuBMAP projects. The Data Analysis Core team has pioneered multiple novel data processing pipelines, including pixel-based analyses, cell-based analyses including state-of- the-art cell segmentation and cell clustering and enumeration, and neighborhood analyses. These tools are broadly-applicable to all highly-multiplexed quantitative imaging technologies. Overall, our team and strategy are exceedingly well-suited for executing the vision of the proposed Bone Marrow TMC. The spatial structure of bone marrow reflects the evolutionary mechanisms that terraformed bone to create unique microenvironments meeting the nutritional needs of developing blood cells with divergent functions. The interdependence between bone marrow tissue structure and hematopoiesis is informative not just in blood cell maturation, but for understanding metabolism, aging, and development of cellular therapies.

项目摘要 - 总体 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）。为了维持和规范这一过程，骨头 骨髓基质细胞形成多个利基微环境，每个环境都根据特定发育的需求而定制 血细胞种群。使用高度插图的成像技术，我们提出的骨髓组织 映射中心（TMC）的目的是系统地剖析细胞组成和空间 人体骨髓微环境的组织。由此产生的详细地图将作为开放和 了解哪些细胞和相互作用对于造血的每个分支至关重要的全球平台 成熟，以及它们如何因解剖部位以及在潜水员的患者人群中的变化。 TMC将在转录，翻译和后的转录，翻译和细胞状态定义细胞身份和细胞态。 使用纳米弦DSP，多路复用离子束成像（MIBI）和MALDI-MSI的翻译水平，它们 分别生成RNA，蛋白质和N-聚糖的定量空间图。我们的跨学科团队不 仅包括Mibi的发明者和Maldi-MSI的先驱，但还包括人类HSC和人类的专家 造血症和具有组织病理学骨髓诊断方面专业知识的练习血管病医生。到 克服使用坚硬，矿化骨骼的独特挑战，我们将利用平行，健壮， 临床上验证的骨髓加工管道最大和标准化样品质量和 与当前和未来技术的兼容性。将无缝集成到标准的临床工作流程中 管道可以使前瞻性收集的材料与组织核心方便地共享。样本将是 从三种不同的来源收集：（1）死者的预期，患者匹配的多站点收集 捐助者检查解剖部位之间的差异，（2）臀部的前瞻性收集股骨头 关节置换术标本的年龄范围之间的差异，（3）斯坦福病理学中的iLiac Crest骨骼档案 种族和性别之间的差异。这些多个收集策略，多个站点和不同的 调查重点补充先前的Hubmap项目。数据分析核心团队已经开创了 多个新型数据处理管道，包括基于像素的分析，基于细胞的分析，包括 ART细胞分割，细胞聚类和枚举以及邻里分析。这些工具是 可广泛适用于所有高度多重的定量成像技术。总体而言，我们的团队和策略是 非常适合执行拟议的骨髓TMC的视力。 骨髓的空间结构反映了骨形成骨的进化机制 独特的微环境满足具有不同功能发育的血细胞的营养需求。这 骨髓组织结构和造血之间的相互依赖性不仅在血细胞中有用 成熟，但用于了解细胞疗法的代谢，衰老和发展。

项目成果

Rapid Setup of Tissue Microarray and Tiled Area Imaging on the Multiplexed Ion Beam Imaging Microscope using the Tile/SED/Array Interface.

使用 Tile/SED/Array 接口在多重离子束成像显微镜上快速设置组织微阵列和平铺区域成像。

• DOI: 10.3791/65615
• 发表时间: 2023
• 期刊: Journal of visualized experiments : JoVE
• 作者: Piyadasa,Hadeesha;Oberlton,Benjamin;Kong,Alex;CamachoFullaway,Christine;ReddyVarra,Sricharan;Sowers,Cameron;Tsai,AlbertG
• 通讯作者: Tsai,AlbertG