Study the roles of p53 and p53 mutants in mesenchymal stem cells

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After we have learned a great deal about the roles of p53 in ES cells in the past four years, my team initiated a project to study the roles of p53 in mesenchymal stem cells (MSCs) in FY2013. Because MSCs are a type of adult stem cells, we believe that this new project complements our existing studies in ES cells, an excellent model to study early development. This initiative aligns well with the mission of the National Cancer Institute (NCI). To effectively address the challenges in the field of MSCs, I have drawn a roadmap for this new project. Using flow cytometry, we have successfully isolated a population of multi-potent cells from mouse bone marrow. These primary cells are able to carry out tri-lineage differentiation, becoming osteoblasts, adipocytes, and chondrocytes under inductive conditions. Our preliminary results showed that p53 plays a role in controlling the osteogenesis of these cells. We will build upon these encouraging results and use RNA-seq combined with single cell analysis to further dissect the sub-populations of the multi-potent cells isolated from mouse bone marrow. We also plan to delineate the molecular mechanism underlying the lineage control of these cells by p53. We are now in the process of comparing the gene signature in MSCs to that in osteosarocma cells and hope to understand how MSCs are related to the initiation and progression of osteosarcoma.