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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC011504-01
Application #
8763574
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2013
Total Cost
$524,002
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
He, Yunlong; de Castro, Luis F; Shin, Min Hwa et al. (2015) p53 loss increases the osteogenic differentiation of bone marrow stromal cells. Stem Cells 33:1304-19
Zhang, Xinyue; He, Yunlong; Lee, Kyoung-Hwa et al. (2013) Rap2b, a novel p53 target, regulates p53-mediated pro-survival function. Cell Cycle 12:1279-91
Li, Mangmang; He, Yunlong; Feng, Xi et al. (2012) Genome-wide studies of the transcriptional regulation by p53. Biochim Biophys Acta 1819:684-7
He, Yunlong; Korboukh, Ilia; Jin, Jian et al. (2012) Targeting protein lysine methylation and demethylation in cancers. Acta Biochim Biophys Sin (Shanghai) 44:70-9
Li, Mangmang; He, Yunlong; Dubois, Wendy et al. (2012) Distinct regulatory mechanisms and functions for p53-activated and p53-repressed DNA damage response genes in embryonic stem cells. Mol Cell 46:30-42