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Organ Specific Project - Bone Marrow

器官特定项目 - 骨髓

基本信息

批准号：
10118853
负责人：
KATHRIN M BERNT
金额：
$ 44.04万
依托单位：
CHILDREN'S HOSP OF PHILADELPHIA
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-01 至 2022-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10118853
关键词：
3-Dimensional Address Adipocytes Aging Anatomy Archives Autopsy Biological Assay Biology Blood Cells Blood Vessels Bone Banks Bone Growth Bone Marrow Bone Marrow Cells Bone Tissue Cell Nucleus Cells Cellular Assay Chromatin Clinical Collection Communities Complex Consent Data Detection Development Disease Doctor of Philosophy Endothelium Epidemiology Epigenetic Process Extracellular Matrix Female Fluorescent in Situ Hybridization Future Genetic Transcription Genomics Goals Heart Hematopoiesis Hematopoietic Hematopoietic stem cells Histologic Homeostasis Human Human BioMolecular Atlas Program Image Infrastructure Knowledge Leadership Location Longevity Lymphoid Mesenchymal Mesenchymal Stem Cells Metadata Minerals Multiomic Data Myelogenous Organ Osteoblasts Osteocytes Osteogenesis Persons Pilot Projects Play Proteomics Protocols documentation Regulator Genes Research Resolution Role Sampling Series Signal Pathway Small Nuclear RNA Specimen Sternum Stromal Cells System Three-Dimensional Imaging Tissues Transposase age group base biobank bone cell type cellular imaging design epigenome experience indexing inter-individual variation male mechanical properties member microCT multiple omics progenitor programs serial imaging transcriptome transcriptome sequencing transcriptomics

项目摘要

PROJECT SUMMARY – BONE ORGAN SPECIFIC PROJECT The bone is a highly complex organ made of three tissue types with distinct functions, including cells from hematopoietic, mesenchymal and endothelial lineages. Confined within one organ and thoroughly mixed with each other, these three tissues are mutually dependent for their development and homeostasis. The spatial organization of the various cell types and their cross-talk in the bone is a major gap of our knowledge. The goal of the bone Organ Specific Project (B-OSP) is to address this knowledge gap and generate high quality, single- cell resolution, longitudinal imaging and multi-omics data of normal bones across the human lifespan. We propose the following three specific aims: 1) To refine protocols for biospecimen processing, multi-omics and imaging assays and define inter-individual variability using our existing banked bone samples. Using existing biobanked normal bones from the autopsy program, we will perform a series of pilot studies to refine our protocols for biospecimen collection and processing, as well as single-cell omics and imaging assays. 2) To procure, archive, and annotate high-quality normal bone samples across human life span. We have established a streamlined procurement and biorepository infrastructure to support our bone OSP. We will procure normal bone from the same donor of 6 age groups across the human life span. 3) To spatially profile bone specimens across the human life span using a set of robust and scalable imaging and single-cell omics assays. We will use micro computed tomography to image every bone we collect at both the macroscale and mesoscale. At the microscale, we will perform single-nucleus RNA sequencing (snRNA-Seq) and single-cell assay for transposase-accessible chromatin using sequencing (scATAC-Seq) of two strategic anatomical sites per bone to determine cell type composition, as well as transcriptional and epigenetic signatures. We will perform multiplexed error-robust fluorescence in situ hybridization (MERFISH, for transcriptomics) and Co- Detection by Indexing (CODEX, for proteomics) analyses.

项目总结-骨器官特定项目骨骼是一个高度复杂的器官，由三种具有不同功能的组织组成，包括来自造血、间充质和内皮谱系。局限在一个器官内，并与这三种组织相互依赖，以实现其发育和体内平衡。空间各种细胞类型的组织和它们在骨骼中的相互作用是我们知识的一个主要空白。目标骨器官特异性项目（B-OSP）的目的是解决这一知识差距，并产生高质量的，单一的，细胞分辨率、纵向成像和人类寿命期间正常骨骼的多组学数据。我们提出以下三个具体目标：1）完善生物标本处理、多组学和成像分析和定义个体间变异使用我们现有的库存骨样本。使用现有从尸检程序中提取正常骨骼的生物样本，我们将进行一系列的试点研究，以完善我们的生物样本收集和处理的协议，以及单细胞组学和成像分析。2)到获取、存档和注释整个人类生命周期的高质量正常骨样本。我们有建立了简化的采购和生物储存基础设施，以支持我们的骨OSP。我们将从6个年龄段的同一供体中获得正常骨。3)空间剖面使用一组强大且可扩展的成像和单细胞组学，分析。我们将使用微型计算机断层扫描技术对我们收集的每一块骨骼进行宏观和微观的成像，中尺度在微尺度上，我们将进行单核RNA测序（snRNA-Seq）和单细胞测序。使用两个关键解剖学位点的测序（scATAC-Seq）测定转座酶可接近的染色质以确定细胞类型组成以及转录和表观遗传特征。我们将进行多重错误鲁棒荧光原位杂交（MERFISH，用于转录组学）和Co- 索引检测（CODEX，用于蛋白质组学）分析。