Browse > Article
http://dx.doi.org/10.5352/JLS.2020.30.4.394

Reversine, Cell Dedifferentiation and Transdifferentiation  

Moon, Yang Soo (Department of Animal Science and Biotechnology, Gyeongnam National University of Science and Technology)
Publication Information
Journal of Life Science / v.30, no.4, 2020 , pp. 394-401 More about this Journal
Abstract
As embryonic stem cells become pluripotent, they may cause tumor development when injected into a host. Therefore, researchers are focusing heavily on the therapeutic potential of tissue-specific stem cells (adult stem cells) without resultant tumor formation. Adult stem cells can proliferate for a limited number of generations and are restricted to certain cell types (multipotent). Mature tissue cell types in mammals cannot be intrinsically dedifferentiated or transdifferentiated to adult stem cells. Hence, the technology of induced pluripotent stem cells (iPSCs) for reprogramming adult somatic cells was introduced in 2006, ushering in a new era in adult stem cell research. Although iPSCs have been widely used in the field, the approach has several limitations: instability of the reprogramming process, risk of incomplete reprogramming, and exposure to transgenes integrated into the cell genome. Two years before the introduction of the iPSC technique, the synthetic small molecule 2,6-disubstituted purine, called reversine, was introduced. Reversine can induce the dedifferentiation of committed cells into multipotent progenitor-type cells by reprogramming and converting adult cells to other cell types under appropriate stimuli. Thus, it can be used as a chemically induced multipotent cell agent to overcome the limitations of iPSCs. Also, as an alternative therapeutic approach for treating obesity, it can be used to generate beige cells by browning white adipocytes. While reversine has the potential to act as an anti-cancer agent, this review focuses on its role in differentiation, dedifferentiation, and transdifferentiation in somatic cells.
Keywords
Dedifferentiation; reprogramming; reversine; somatic cells; transdifferentiation;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Lv, X., Zhu, H., Bai, Y., Chu, Z., Hu, Y., Cao, H., Liu, C., He, X., Peng, S., Gao, Z., Yang, C. and Hua, J. 2012. Reversine promotes porcine muscle derived stem cells (PMDSCs) differentiation into female germ-like cells. J. Cell Biochem. 113, 3629-3642.   DOI
2 Miyoshi, K., Mori, H., Mizobe, Y., Himaki, T., Yoshida, M. and Sato, M. 2010. Beneficial effects of reversine on in vitro development of miniature pig somatic cell nuclear transfer embryos. J. Reprod. Dev. 56, 291-296.   DOI
3 Park, J. G., Lee, D. H., Moon, Y. S. and Kim, K. H. 2014. Reversine increases the plasticity of lineage-committed preadipocytes to osteogenesis by inhibiting adipogenesis through induction of TGF-$\beta$ pathway in vitro. Biochem. Biophys. Res. Commun. 446, 30-36.   DOI
4 Piccoli, M., Ghiroldi, A., Monasky, M. M., Cirillo, F., Ciconte, G., Pappone, C. and Anastasia, L. 2019. Reversine: A synthetic purine with a dual activity as a cell dedifferentiating agent and a selective anticancer drug. Curr. Med. Chem. doi:10.2174/0929867326666190103120725.
5 Piccoli, M., Palazzolo, G., Conforti, E., Lamorte, G., Papini, N., Creo, P., Fania, C., Scaringi, R., Bergante, S., Tringali, C., Roncoroni, L., Mazzoleni, S., Doneda, L., Galli, R., Venerando, B., Tettamanti, G., Gelfi, C. and Anastasia, L. 2012. The synthetic purine reversine selectively induces cell death of cancer cells. J. Cell Biochem. 113, 3207-3217.   DOI
6 Pikir, B. S., Susilowati, H., Hendrianto, E. and Abdulrantam, F. 2012. Reversin increase the plasticity of bone marrow-derived mesenchymal stem cell for generation of cardiomyocyte in vitro. Acta Med. Indones. 44, 23-27.
7 Anastasia, L., Pelissero, G., Venerando, B. and Tettamanti, G. 2010. Cell reprogramming: expectations and challenges for chemistry in stem cell biology and regenerative medicine. Cell Death Differ. 17, 1230-1237.   DOI
8 Anastasia, L., Sampaolesi, M., Papini, N., Oleari, D., Lamorte, G., Tringali, C., Monti, E., Galli, D., Tettamanti, G., Cossu, G. and Venerando, B. 2006. Reversine-treated fibroblasts acquire myogenic competence in vitro and in regenerating skeletal muscle. Cell Death Differ. 13, 2042-2051.   DOI
9 Brockes, J. P. and Kumar, A. 2002. Plasticity and reprogramming of differentiated cells in amphibian regeneration. Nat. Rev. Mol. Cell Biol. 3, 566-574.   DOI
10 Chen, S., Takanashi, S., Zhang, Q., Xiong, W., Zhu, S., Peters, E. C., Ding, S. and Schultz, P. G. 2007. Reversine increases the plasticity of lineage-committed mammalian cells. Proc. Natl. Acad. Sci. USA. 104, 10482-10487.   DOI
11 Chen, S., Zhang, Q., Wu, X., Schultz, P. G. and Ding, S. 2004. Dedifferentiation of lineage-committed cells by a small molecule. J. Am. Chem. Soc. 126, 410-411.   DOI
12 Conforti, E., Arrigoni, E., Piccoli, M., Lopa, S., de Girolamo, L., Ibatici, A., Di Matteo, A., Tettamanti, G., Brini, A. T. and Anastasia, L. 2011. Reversine increases multipotent human mesenchymal cells differentiation potential. J. Biol. Regul. Homeost. Agents. 25, S25-33.
13 Kim, M., Yi, S. A., Lee, H., Bang, S. Y., Park, E. K., Lee, M. G., Nam, K. H., Yoo, J. H., Lee, D. H., Ryu, H. W., Kwon, S. H. and Han, J. W. 2014. Reversine induces multipotency of lineage-committed cells through epigenetic silencing of miR-133a. Biochem. Biophys. Res. Commun. 445, 255-262.   DOI
14 Kim, S., Park, J. W., Lee, M. G., Nam, K. H., Park, J. H., Oh, H., Lee, J., Han, J., Yi, S. A. and Han, J. W. 2019. Reversine promotes browning of white adipocytes by suppressing miR-133a. J. Cell Physiol. 234, 3800-3813.   DOI
15 Kim, M., Yi, S. A., Lee, H., Bang, S. Y., Park, E. K., Lee, M. G., Nam, K. H., Yoo, J. H., Lee, D. H., Ryu, H. W., Kwon, S. H. and Han, J. W. 2014. Reversine induces multipotency of lineage-committed cells through epigenetic silencing of miR-133a. Biochem. Biophys. Res. Commun. 445, 255-262.   DOI
16 Kim, Y. K., Choi, H. Y., Kim, N. H., Lee, W., Seo, D. W., Kang, D. W., Lee, H. Y., Han, J. W., Park, S. W. and Kim, S. N. 2007. Reversine stimulates adipocyte differentiation and downregulates Akt and p70 (s6k) signaling pathways in 3T3-L1 cells. Biochem. Biophys. Res. Commun. 358, 553-558.   DOI
17 Shan, S. W., Tang, M. K., Chow, P. H., Maroto, M., Cai, D. Q. and Lee, K. K. 2007. Induction of growth arrest and polycomb gene expression by reversine allows C2C12 cells to be reprogrammed to various differentiated cell types. Proteomics 7, 4303-4316.   DOI
18 Lee, E. K., Bae, G. U., You, J. S., Lee, J. C., Jeon, Y. J., Park, J. W., Park, J. H., Ahn, S. H., Kim, Y. K., Choi, W. S., Kang, J. S., Han, G. and Han, J. W. 2009. Reversine increases the plasticity of lineage-committed cells toward neuroectodermal lineage. J. Biol. Chem. 284, 2891-2901.   DOI
19 Li, X., Guo, Y., Yao, Y., Hua, J., Ma, Y., Liu, C. and Guan, W. 2016. Reversine increases the plasticity of long-term cryopreserved fibroblasts to multipotent progenitor cells through activation of Oct4. Int. J. Biol. Sci. 12, 53-62.   DOI
20 Saraiya, M., Nasser, R., Zeng, Y., Addya, S., Ponnappan, R. K., Fortina, P., Anderson, D. G., Albert, T. J., Shapiro, I. M. and Risbud, M. V. 2010. Reversine enhances generation of progenitor-like cells by dedifferentiation of annulus fibrosus cells. Tissue Eng. Part A. 16, 1443-1455.   DOI
21 Soltani, L., Rahmani, H. R., Daliri Joupari, M., Ghaneialvar, H., Mahdavi, A. H. and Shamsara, M. 2016. Ovine fetal mesenchymal stem cell differentiation to cardiomyocytes, effects of co-culture, role of small molecules; reversine and 5-azacytidine. Cell Biochem. Funct. 34, 250-261.   DOI
22 Soltani L, Rahmani, H. R., Daliri Joupari, M., Ghaneialvar, H., Mahdavi, A. H. and Shamsara, M. 2020. Effects of different concentrations of reversine on plasticity of mesenchymal stem cells. Indian J. Clin. Biochem. 35, 188-196.   DOI
23 Tsonis, P. A. 2004. Stem cells from differentiated cells. Mol. Interv. 4, 81-83.   DOI
24 Takahashi, K. and Yamanaka, S. 2006. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126, 663-676.   DOI