The Bone Marrow Multi-modal Imaging Core

项目摘要-机关特定项目

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.