Identification and Manipulation of HSC Niche Components
Intravital 2-photon imaging of mouse calvaria (Blue: Collagen;
Green: CFSE labeled Cells; Red: Dextran-Texas Red labeled blood vessels)
Hematopoiesis and hematopoietic stem cells are dependent upon regulation from the bone marrow microenvironment. The specific components of the bone marrow required for HSC support have been termed the HSC niche. Our laboratory and others have previously identified multiple cellular niche components that include osteolineage cells, endothelial cells, mesenchymal stem cells and adipocytes. Ongoing research projects in our lab are continuing to define the roles individual niche components play within the larger, complex network of the HSC niche, and to identify pharmacologic strategies to manipulate the HSC niche. We are interested in both cellular as well as molecular mechanisms involved in HSC-niche interactions. We utilize both murine models and primary human samples of normal, aged and diseased individuals. To achieve these goals we utilize several genetically altered mouse models, and state of the art techniques including: intravital imaging, mass cytometry (CyTOF), multiparameter flow cytometric analysis and cell sorting, luminex, and RNA sequencing. Our work has identified critical osteoblastic-endothelial interactions during niche stimulation, and defined the role of the Notch ligand Jagged1 as a crucial regulator of osteolineage cell maturation and function. Our goal is to continue to dissect fundamental microenvironmental signals that may be amenable to human translation.