Project Summary This application is from the Nebraska Research Network in Functional Genomics (NE-INBRE) in response to NOT-GM-24-001 regarding the availability of administrative supplements to IDeA Awards to Fund Team Science Development Projects. We have assembled a team of four Nebraska investigators with diverse and complementary backgrounds and expertise who will use cutting edge bioinformatic and human organoid approaches to investigate the molecular mechanisms regulating human hematopoiesis and bone related disease. Hematopoietic Stem Cells (HSCs) are governed by numerous positive and negative feedback signals within the bone marrow niche. The crosstalk between HSCs and cells in the microenvironment is critical for efficient production of blood cells and when it is perturbed, as with diseases like cancer, it can have serious consequences. However, the molecular mechanism regulating this interaction are not well understood and are difficult to model ex vivo. This project will combine expertise in hematopoiesis and bone marrow biology with state-of-the-art human bone marrow organoids and cutting edge genomic and bioinformatic analysis with a team science approach to address one of the main themes of the NE-INBRE. Goals of the Parent Award: The Nebraska Research Network in Functional Genomics (NE-INBRE) is aimed at developing the biomedical research capacity at institutions of higher education in Nebraska. The NE-INBRE is structured around two major components: Primary Undergraduate Institutions (PUIs) and PhD granting Research Institutions (RIs). Support for each PUI consists of: 1) campus research capacity development through support for faculty research and infrastructure enhancement, and 2) development of the undergraduate research pipeline of students through the NE-INBRE Scholars Program. Two features are associated with expanding research capacity at the RIs: 1) Providing significant support to multi-user core facilities in order to allow investigators from PUIs and RIs access to cutting-edge technology, and 2) providing support in the form of first-year graduate assistantships for NE-INBRE scholars who matriculate into PhD programs at the RI campuses. The three participating RIs in the research network include two campuses of the University of Nebraska system and one privately supported medical center. Cutting edge multi-user core facilities include cores in genomics, bioinformatics, and imaging. The three themes reflect the scientific foci of the NE-INBRE: cancer, cell signaling, and infectious disease. These themes serve to link faculty and students at the separate institutions into productive networks based on their areas of expertise and interest. Research Question to be addressed in the Supplement Proposal: Until recently, the major limitation in dissecting the complex interactions between the HSCs and the microenvironment has been the lack of suitable models. Traditional ex vivo co-culturing approaches do not replicate the compl...