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

研究p53和p53突变体在间充质干细胞中的作用

• 批准号: 8938166
• 负责人: Jing Huang
• 金额: $ 54.21万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8938166
• 关键词: Address; Adipocytes; Adolescent; Affect; Behavior; Biological Assay; Bone Marrow; Bone Marrow Cells; Cell Therapy; Cell surface; Cells; Chondrocytes; Complement; Development; Flow Cytometry; Genes; Goals; Heterogeneity; Homeostasis; In Vitro; Learning; Malignant Neoplasms; Mesenchymal Stem Cells; Methods; Mission; Modeling; Molecular; Mus; National Cancer Institute; Oncogenes; Osteoblasts; Osteogenesis; Play; Population; Process; Research Personnel; Risk; Role; Signal Transduction; Techniques; Testing; Tissues; Umbilical Cord Blood; adult stem cell; base; bone; cancer type; combat; embryonic stem cell; in vivo; insight; mutant; novel; novel strategies; osteosarcoma; single cell analysis; technique development; time use; transcriptome sequencing; tumor; tumorigenic

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.

在过去的四年中，我们已经了解了大量关于p53在ES细胞中的作用，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（MSC）中的作用。由于MSC是一种成体干细胞，我们相信这个新项目补充了我们现有的ES细胞研究，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。为了有效地应对MSC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，我们已经成功地从小鼠骨髓中分离出一群多能细胞。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在控制这些细胞的成骨中起作用。我们将在这些令人鼓舞的结果的基础上，使用RNA-seq与单细胞分析相结合，进一步剖析从小鼠骨髓中分离的多能细胞的亚群。我们还计划描绘这些细胞的谱系控制p53的分子机制。我们现在正在比较骨髓间充质干细胞和骨肉瘤细胞的基因特征，希望了解骨髓间充质干细胞与骨肉瘤的发生和发展的关系。