Multimodal histologic atlas of human bone marrow

人骨髓多模态组织学图谱

• 批准号: 10531005
• 负责人: Robert michael Angelo
• 金额: $ 150万
• 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/10531005
• 关键词: Affect; Age; Aging; Anatomy; Antibodies; Archives; Atlases; Biological; Biological Assay; Blood Cells; Blood Group Antigens; Bone Marrow; Bone Marrow Cells; Bone structure; Caliber; Cell Communication; Cell Maturation; Cell Therapy; Cells; Clinical; Collection; Communities; Complement; DNA; Data; Data Analyses; Data Set; Diagnosis; Doctor of Philosophy; Ensure; Erythroid; Future; Gender; Genetic Transcription; Goals; Head; Hematopoiesis; Hematopoietic; Hematopoietic stem cells; Hemostatic function; Histologic; Human; Human BioMolecular Atlas Program; Image; Imaging technology; Investigation; Length; Maps; Marrow; Metabolism; Minerals; Modality; Morphology; Multiplexed Ion Beam Imaging; Neighborhoods; Nutritional; Oligonucleotides; Oxygen; Pathologist; Pathology; Patients; Phenotype; 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; base; bone; cellular development; cohort; computerized tools; data analysis pipeline; data pipeline; demographics; ethnic diversity; hip replacement arthroplasty; human tissue; imaging modality; mass spectrometric imaging; meetings; multimodality; multiplexed imaging; nano-string; novel; preservation; progenitor; programs; prospective; quantitative imaging; rib bone structure; sample collection; spine bone structure; tissue archive; 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.

项目总结 – 总体 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），为了维持和调节这个过程，骨骼。 骨髓基质细胞形成多个生态位微环境，每个微环境都根据特定发育的需要而定制 使用高度多重成像技术，我们提出了骨髓组织。 制图中心（TMC）旨在系统、定量地剖析细胞组成和空间 人类骨髓微环境的组织由此产生的详细图谱将作为一个开放和 用于了解哪些细胞和相互作用对于造血每个分支至关重要的全球平台 成熟度，以及这些随着解剖部位和不同患者人口统计数据的不同而变化。 TMC 将定义转录、翻译和后期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 进行翻译水平， 我们的跨学科团队没有分别生成 RNA、蛋白质和 N-聚糖的定量空间图。 不仅包括MIBI的发明者和MALDI-MSI的先驱，还包括人类HSC和人类的专家 造血学和具有组织病理学骨髓诊断专业知识的执业血液病理学家。 克服处理坚硬、矿化骨骼的独特挑战，我们将利用平行、稳健、 经过临床验证的骨髓处理管道，可最大限度地提高和标准化样本质量， 我们的技术与当前和未来的技术无缝集成到标准临床工作流程中。 管道可以方便地与组织核心样本共享预期收集的材料。 从三个不同来源收集：（1）前瞻性、患者匹配的多地点死者收集 供体检查解剖部位之间的差异，（2）从髋部前瞻性收集股骨头 不同年龄范围之间差异的关节成形术标本，(3) 斯坦福病理学档案中的髂嵴骨 这些多种收集策略、多个地点和不同的差异。 研究重点补充了数据分析核心团队开创的先前 HuBMAP 项目。 多种新颖的数据处理流程，包括基于像素的分析、基于细胞的分析，包括状态分析 最先进的细胞分割、细胞聚类和计数以及邻域分析是这些工具。 总体而言，我们的团队和策略广泛适用于所有高度多重定量成像技术。 非常适合执行拟议的骨髓 TMC 的愿景。 骨髓的空间结构反映了骨骼改造的进化机制 独特的微环境满足具有不同功能的血细胞发育的营养需求。 骨髓组织结构和造血之间的相互依赖性不仅在血细胞中提供信息 成熟，而是为了了解新陈代谢、衰老和细胞疗法的发展。