Single Cell Spatial Characterization of the Human Bone Marrow Microenvironment

人类骨髓微环境的单细胞空间表征

• 批准号: 10115110
• 负责人: Daniel C Link
• 金额: $ 19.69万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-01 至 2022-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10115110
• 关键词: Aging; Animal Model; Antibodies; Architecture; Biological Assay; Bone Marrow; Cell Communication; Cell Surface Proteins; Cells; Cellular Indexing of Transcriptomes and Epitopes by Sequencing; Cytometry; Data; Data Analyses; Detection; Disease; Endothelial Cells; Formalin; Future; Gender; Gene Expression; Genes; Geography; Glean; Goals; Hematopoiesis; Hematopoietic; Hematopoietic Neoplasms; Hematopoietic stem cells; Heterogeneity; Human; Image; Investigation; Maps; Mesenchymal; Methods; Morphology; Mus; Nerve; Oligonucleotides; Osteoblasts; Paraffin Embedding; Patients; Pericytes; Phenotype; Physiological; Population; Population Heterogeneity; Proteins; Regulation; Research; Resolution; Schwann Cells; Signal Transduction; Stains; Stress; Stromal Cells; Structure; Surface; Technology; Time; Tissues; base; bone; genetic manipulation; healthy volunteer; hematopoietic stem cell niche; high dimensionality; insight; interest; mesenchymal stromal cell; mouse model; novel; novel marker; progenitor; protein biomarkers; protein expression; response; self-renewal; single-cell RNA sequencing; stem; stem cell function; stem cell proliferation; trafficking; transcriptome

Project Summary/Abstract The objective of this project is to utilize high dimensional single cell approaches to delineate the spatial architecture of human bone marrow. Functions of hematopoietic stems cells are known to be modulated by signals generated by stromal cells in the bone marrow. Geographic relationships between hematopoietic cells and specific stromal cell populations are thought to be a critical component of this interaction. While studies in animal models have elucidated many of these key relationships, similar studies in human bone marrow have been limited. We therefore propose to utilize imaging mass cytometry (IMC) to directly interrogate the cellular architecture of the human bone marrow microenvironment. We will couple this approach with single cell RNA sequencing to enable the identification of novel markers of specific stromal cell populations. These findings will be leveraged to further inform the IMC approach. Within this context, we will develop a road map of normal human bone marrow, which can serve as the framework for subsequent studies of both normal and diseased hematopoietic states.

项目总结/摘要 本项目的目标是利用高维单细胞方法来描绘空间 人类骨髓的结构。已知造血干细胞的功能受到以下因素的调节： 由骨髓基质细胞产生的信号。造血细胞之间的地理关系 并且特异性基质细胞群被认为是这种相互作用的关键组分。虽然研究在 动物模型已经阐明了这些关键关系中的许多，在人类骨髓中的类似研究已经 被限制。因此，我们建议利用成像质谱细胞仪（IMC）直接询问细胞的 人骨髓微环境的结构。我们将把这种方法与单细胞RNA结合起来， 测序以鉴定特异性基质细胞群的新标志物。这些发现将 进一步为IMC方法提供信息。在这一背景下，我们将制定一个正常 人骨髓，它可以作为正常和疾病的后续研究的框架， 造血状态