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

在过去的四年里，我们对P53在ES细胞中的作用有了大量的了解后，我的团队在2013财年启动了一个项目，研究P53在间充质干细胞(MSCs)中的作用。因为MSCs是一种成体干细胞，我们相信这个新的项目是对我们现有的ES细胞研究的补充，ES细胞是研究早期发育的一个很好的模型。这一倡议与国家癌症研究所(NCI)的使命非常一致。为了有效应对MSCS领域的挑战，我为这个新项目绘制了路线图。利用流式细胞术，我们成功地从小鼠骨髓中分离出了一批多能细胞。这些原代细胞能够进行三系分化，在诱导条件下成为成骨细胞、脂肪细胞和软骨细胞。我们的初步结果表明，P53在这些细胞的成骨过程中起着控制作用。我们将在这些令人鼓舞的结果的基础上，使用RNA-SEQ结合单细胞分析来进一步剖析从小鼠骨髓中分离的多潜能细胞的亚群。我们还计划描述P53控制这些细胞谱系的分子机制。我们现在正在比较MSCs和骨肉瘤细胞中的基因特征，并希望了解MSCs如何与骨肉瘤的发生和发展有关。

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.