p53 regulates the proliferation, differentiation and spontaneous transformation of mesenchymal stem cells.
Mesenchymal stem cells (MSC) have been extensively studied and gained wide popularity due to their therapeutic potential. Spontaneous transformation of MSC, from both human and murine origin, has been reported in many studies. MSC transformation depends on the culture conditions, the origin of the cells and the time on culture; however, the precise biological characteristics involved in this process have not been fully defined yet. In this study, we investigated the role of p53 in the biology and transformation of murine bone marrow (BM)-derived MSC. We demonstrate that the MSC derived from p53KO mice showed an augmented proliferation rate, a shorter doubling time and also morphologic and phenotypic changes, as compared to MSC derived from wild-type animals. Furthermore, the MSC devoid of p53 had an increased number of cells able to generate colonies. In addition, not only proliferation but also MSC differentiation is controlled by p53 since its absence modifies the speed of the process. Moreover, genomic instability, changes in the expression of c-myc and anchorage independent growth were also observed in p53KO MSC. In addition, the absence of p53 implicates the spontaneous transformation of MSC in long-term cultures. Our results reveal that p53 plays a central role in the biology of MSC.
Armesilla-Diaz
Alejandro
A
Department of Cellular and Molecular Physiopathology, Centro de Investigaciones Biológicas, CSIC, Ramiro de Maeztu, 9, 28040 Madrid, Spain. aarmesilla@cib.csic.es
Elvira
Gema
G
Silva
Augusto
A
D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D003114:Colony-Forming Units Assay; D004268:DNA-Binding Proteins / Q000235:genetics; D015870:Gene Expression / Q000235:genetics; D042822:Genomic Instability / Q000235:genetics; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D011123:Polyploidy; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D051135:Rad51 Recombinase / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
D000943:Antigens, Differentiation; D004268:DNA-Binding Proteins; C489428:Myc protein, mouse; D016271:Proto-Oncogene Proteins c-myc; C499308:Rag2 protein, mouse; D016159:Tumor Suppressor Protein p53; D051135:Rad51 Recombinase; C495154:Rad51 protein, mouse