Characterization of common marmoset dysgerminoma‐like tumor induced by the lentiviral expression of reprogramming factors |
| |
| Authors: | Saori Yamaguchi Tomotoshi Marumoto Takenobu Nii Hirotaka Kawano Jiyuan Liao Yoko Nagai Michiyo Okada Atsushi Takahashi Hiroyuki Inoue Erika Sasaki Hiroshi Fujii Shinji Okano Hayao Ebise Tetsuya Sato Mikita Suyama Hideyuki Okano Yoshie Miura Kenzaburo Tani |
| |
| Affiliation: | 1. Division of Molecular and Clinical Genetics, Molecular and Clinical Genetics, Medical Institute of Bioregulation, Kyushu University, , Fukuoka, Japan;2. Department of Advanced Molecular and Cell Therapy, Kyushu University Hospital, , Fukuoka, Japan;3. Division of Translational Cancer Research Medical Institute of Bioregulation, Kyushu University, , Fukuoka, Japan;4. KEIO‐RIKEN Research Center for Human Cognition, Keio University, , Tokyo, Japan;5. Division of Pathophysiological and Experimental Pathology, Department of Pathology, Kyushu University, , Fukuoka, Japan;6. Genomic Science Laboratories, Dainippon Sumitomo Pharma, , Osaka, Japan;7. Division of Bioinformatics, Medical Institute of Bioregulation, Kyushu University, , Fukuoka, Japan;8. Department of Physiology, Keio University, , Tokyo, Japan |
| |
| Abstract: | Recent generation of induced pluripotent stem (iPSCs) has made a significant impact on the field of human regenerative medicine. Prior to the clinical application of iPSCs, testing of their safety and usefulness must be carried out using reliable animal models of various diseases. In order to generate iPSCs from common marmoset (CM; Callithrix jacchus), one of the most useful experimental animals, we have lentivirally transduced reprogramming factors, including POU5F1 (also known as OCT3/4), SOX2, KLF4, and c-MYC into CM fibroblasts. The cells formed round colonies expressing embryonic stem cell markers, however, they showed an abnormal karyotype denoted as 46, X, del(4q), +mar, and formed human dysgerminoma-like tumors in SCID mice, indicating that the transduction of reprogramming factors caused unexpected tumorigenesis of CM cells. Moreover, CM dysgerminoma-like tumors were highly sensitive to DNA-damaging agents, irradiation, and fibroblast growth factor receptor inhibitor, and their growth was dependent on c-MYC expression. These results indicate that DNA-damaging agents, irradiation, fibroblast growth factor receptor inhibitor, and c-MYC-targeted therapies might represent effective treatment strategies for unexpected tumors in patients receiving iPSC-based therapy. |
| |
| Keywords: | Common marmoset
FGFR
regenerating medicine reprogramming factor tumorigenesis |
|
|
