Cell and Molecular Dynamics of Hematopoiesis In Vivo

 描述(申请人提供)：本提案旨在通过定义小鼠体内造血干细胞和祖细胞(HSPC)功能异质性的分子基础，为造血学研究社区创建一个独特的生物分子数据集。这将在克隆水平上完成，顺序使用允许克隆跟踪、细胞分离和分子分析的工程小鼠品系。骨髓微环境将在类似条件下进行分析，这些区域物理上接近造血干细胞和祖细胞。结合这个数据集，将提供高度注释的活体细胞在未受干扰和应激条件下行为的全面分子表征。它涉及三名研究人员，他们在造血、生物分子计算和高分辨率活体成像领域拥有独特和互补的专业知识。它涉及到这些研究人员和这些学科之间的互动所产生的独特工具。这一提议的成功完成将产生一种独特的资源，将分子数据与单个造血细胞克隆的功能属性结合起来。这将对该领域有用，并指导其他人未来的研究，以确定干细胞和祖细胞特定功能的分子驱动因素。

 DESCRIPTION (provided by applicant): This proposal seeks to create a unique biomolecular dataset for the hematopoiesis research community by defining the molecular basis for functional heterogeneity among hematopoietic stem and progenitor cells (HSPC) in vivo in the mouse. This will be accomplished at a clonal level, sequentially using an engineered mouse strain that permits clonal tracking, cell isolation and molecular analyses. The bone marrow microenvironment will be analyzed under similar conditions of regions in physical proximity to hematopoietic stem and progenitor cells. Combined this dataset will provide a comprehensive molecular characterization of highly annotated in vivo cell behaviors under unperturbed and stress conditions. It involves three investigators with distinctive and complementary areas of expertise in the field of hematopoiesis, biomolecular computation and high resolution in vivo imaging. It involves distinctive tools generated by the interaction between these investigators and these disciplines. Successful accomplishment of this proposal will result in a unique resource coupling molecular data with functional attributes of individual clones of blood forming cells. It will be useful for the field and guide future studies by others to determine the molecula drivers of specific functions of stem and progenitor cells.