The Bone Marrow Multi-modal Imaging Core

项目摘要-特定于机构的项目 骨髓产生血细胞，其功能范围从氧气输送到抗微生物防御，再到 止血，全部来源于造血干细胞(HSC)。为了维持和规范这一分支 在成熟过程中，骨髓基质细胞形成多个利基微环境，每个微环境都适合 特定发育中的血细胞群体的需求。器官特定项目(OSP)旨在系统地 并定量地解剖了人骨髓的细胞组成和空间组织。 使用高度多路复用成像技术的微环境。生成的详细地图将用作 开放的全球平台，用于了解哪些单元和交互对每个分支机构至关重要 造血成熟。 作为之前HuBMAP项目的补充，OSP将比较来自 解剖位置并检查年龄、性别和种族的影响。样本将由三个不同的人收集 策略，每个策略都有不同的研究重点：(1)预期收集6名死者的骨髓 椎骨、肋骨和胸骨供者检查3个解剖部位的差异，(2)前瞻性 从16个髋关节置换术股骨头标本中收集年龄范围的差异，(3)80个 斯坦福大学病理档案馆诊断正常的髂骨骨髓样本的差异 种族和性别之间的差异。一旦收集到样本，我们将通过现有的临床验证的预先验证的 分析处理管道，以最大限度地兼容当前和未来的分析。 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、多路离子束成像(MIBI)和MALDI-MSI的电平，它们产生 RNA、蛋白质和N-糖链的定量空间图谱。我们的研究团队包括 MIBI，MALDI-MSI的先驱，组织图像处理算法的发明者，人类造血干细胞和 造血学，以及一位常规诊断人类骨髓的执业血液病理学家。集成 结合这些数据，我们将通过以下方式定量和系统地识别骨髓微环境 它们的细胞组成和建筑组织的模式。 比较我们三个队列中的微体系结构将阐明解剖位置、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，以什么方式丢失 地点，以及其中的微环境将提供对人类衰老及其与 新陈代谢和DNA损伤。性别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之类的进化力量。这些见解 然后可以被用来诊断和剖析疾病状态，并设计新的细胞疗法。

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.