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. 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. Therefore, these cells are functionally defined as mesenchymal stem cells (MSCs). Our preliminary results showed that p53 plays a role in controlling the osteogenesis of these MSCs. In addition, we delineated the molecular mechanism underlying the lineage control of these cells by p53. We found that p53 induces miR34s, which suppresses the translation of Runx2 in MSCs. Thus, p53 indirectly represses Runx2, a key transcription regulator of osteogenic differentiation. We have published these observations in Stem Cells (33: 1304-1319, 2015). Because MSCs are one of the cell-of-origins of OS, we plan to study the roles of Runx2 in osteosarcoma cells. Our preliminary results showed that Runx2 is involved in the survival of OS cells. Investigation of this pro-survival function of Runx2 in OS cells is ongoing.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC011504-04
Application #
9343963
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
He, Yunlong; Zhu, Wentao; Shin, Min Hwa et al. (2017) cFOS-SOX9 Axis Reprograms Bone Marrow-Derived Mesenchymal Stem Cells into Chondroblastic Osteosarcoma. Stem Cell Reports 8:1630-1644
Shin, Min Hwa; He, Yunlong; Marrogi, Eryney et al. (2016) A RUNX2-Mediated Epigenetic Regulation of the Survival of p53 Defective Cancer Cells. PLoS Genet 12:e1005884
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; 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
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