A mini review on production of pluripotency factors (Oct4, Sox2, Klf4 and c-Myc) through recombinant protein technology

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David Septian Sumanto Marpaung
Ayu Oshin Yap Sinaga


The four transcription factors OCT4, SOX2, KLF4 and c-MYC are highly expressed in embryonic stem cells (ESC) and their overexpression can induce pluripotency, the ability to differentiate into all cell types of an organism. The ectopic expression such transcription factors could reprogram somatic stem cells become induced pluripotency stem cells (iPSC), an embryonic stem cells-like. Production of recombinant pluripotency factors gain interests due to high demand from generation of induced pluripotent stem cells in regenerative medical therapy recently. This review will focus on demonstrate the recent advances in recombinant pluripotency factor production using various host.


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Marpaung, D. S. S., & Sinaga, A. O. Y. (2020). A mini review on production of pluripotency factors (Oct4, Sox2, Klf4 and c-Myc) through recombinant protein technology. Communications in Science and Technology, 5(1), 1-4. https://doi.org/10.21924/cst.5.1.2020.171


1. B. V. Johnson, N. Shindo, P. D. Rathjen, J. Rathjen, and R. A. Keough, Understanding pluripotency—how embryonic stem cells keep their options open, Mol. Hum. Reprod. 14 (2008) 513-520.
2. A. Trounson, N. D. DeWitt, Pluripotent stem cells progressing to the clinic, Nat. Rev. Mol. Cell Biol. 17 (2016) 194–200.
3. K. Takahashi, S. Yamanaka, Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors, Cell 126 (2006) 663–676.
4. S. Ruiz, O. Fernandez-Capetillo, Reducing genomic instability in iPSCs, Oncotarget. 6 (2015) 34045–34046.
5. A. Harui, S. Suzuki, S. Kochanek, and K. Mitani, Frequency and stability of chromosomal integration of adenovirus vectors, J. Virol. 73 (1999) 6141-6146.
6. K.Woltjen, I. P. Michael, P. Mohseni, R. Desai, M. Mileikovsky, R. Hamalainen, et al., piggyBac transposition reprograms fibroblasts to induced pluripotent stem cells, Nature 458 (2009) 766–770.
7. H. Ban, N. Nishishita, N. Fusaki, T. Tabata, K. Saeki, M. Shikamura, et al., Efficient generation of transgene-free human induced pluripotent stem cells (iPSCs) by temperature-sensitive Sendai virus vectors, Proc. Natl. Acad. Sci. 108 (2011) 14234-14239.
8. L. Warren, P. D. Manos, T. Ahfeldt, Y. H. Loh, H. Li, F. Lau., et al., Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA, Cell Stem Cell 7 (2010) 618–630.
9. P. Hou, Y. Li, X. Zhang, C. Liu, J. Guan, H. Li, et al., Pluripotent stem cells induced from mouse somatic cells by small-molecule compounds, Science 341 (2013) 651–654
10. H. Y. Zhou, S. L. Wu, J. Y. Joo, S. Y. Zhu, D. W. Han, T. X. Lin, et al., Generation of induced pluripotent stem cells using recombinant proteins, Cell Stem Cell 4 (2009) 381–384.
11. D. Kim, C.-H. Kim, J.-I. Moon, Y.-G. Chung, M.-Y. Chang, B.-S. Han, et al., Generation of human induced pluripotent stem cells by direct delivery of reprogramming proteins, Cell Stem Cell 4 (2009) 472-476.
12. S. Stefanovic, M. Pucéat, Oct-3/4: Not just a gatekeeper of pluripotency for embryonic stem cell, a cell fate instructor through a gene dosage effect, Cell Cycle 6 (2007) 8-10.
13. H. Niwa, J. Miyazaki, A. G. Smith, Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells, Nat. Genet. 24 (2000) 372-376.
14. T. Dingermann, Recombinant therapeutic proteins: Production platforms and challenges, Biotechnol. J. 3 (2008) 90-97.
15. S. N. Cohen, A. C. Chang, H. W. Boyer, R. B. Helling, Construction of biologically functional bacterial plasmids in vitro, Proc. Natl. Acad. Sci. USA 70 (1973) 3240-3244.
16. G.-D. Liu, S.-F. Zhou, X.-C. Ding, C.-L. Fang, S.-Y. Mi, X.-C. Gao, Soluble expression of recombinant cMyc, Klf4, Oct4, and Sox2 proteins in bacteria and transduction into living cells, Int. J. Ophthalmol. 10 (2017) 560-566.
17. P. N. Malak, B. Dannenmann, A. Hirth, O. C. Rothfuss, K. Schulze- Osthoff, Novel AKT phosphorylation sites identified in the pluripotency factors Oct4, Sox2 and Klf4, Cell Cycle 14 (2015) 3748-3754.
18. H. Wang, X. Zhang, N. Kong, A. Wei, Y. Zhang, J. Ma, et al, Expression, purification and characterization of a recombinant Tat47-57-Oct4 fusion protein in Pichia pastoris, Mol. Med. Rep. 9 (2014) 471-475.
19. W. Shen, Y. Xue, Y. Liu, C. Kong, X. Wang, M. Huang, A novel methanol-free Pichia pastoris system for recombinant protein expression, Microb. Cell Fact. 15 (2016) 178.
20. S. Tammam, P. Malak, D. Correa, O. Rothfuss, H. M. E. Azzazy, A. Lamprecht, et al., Nuclear delivery of recombinant Oct4 by chitosan nanoparticles for transgene-free generation of protein-induced pluripotent stem cells, Oncotarget. 7 (2016) 37728-37739.
21. D. Cyranoski, Japanese man is first to receive ‘reprogrammed’ stem cells from another person, Nature News. (2017) Available: https://www.nature.com/news/japanese-man-is-first-to-receive-reprogrammed-stem-cells-from-another-person-1.21730 [Accessed: 4-Feb-2020].
22. U. Martin, Therapeutic application of pluripotent stem cells: Challenges and risks, Fron. Med. 4 (2017) 229
23. S. Miersch, S. S. Sidhu, Intracellular targeting with engineered proteins, F1000Research 5 (2016) 1947.
24. E. Koren, V. P. Torchilin, Cell-penetrating peptides: breaking through to the other side, Trends Mol. Med. 18 (2012) 385-393.
25. A. V. Ulasov, A. A. Rosenkranz, A. S. Sobolev, Transcription factors: Time to deliver, J. Control. Release 269 (2018) 24-35
26. A. D. Frankel, C. O. Pabo, Cellular uptake of the tat protein from human immunode?ciency virus, Cell 55 (1988) 1189-1193
27. S. Futaki, T. Suzuki, W. Ohashi, T. Yagami, S. Tanaka, K. Ueda, Y. Sugiura, Arginine-rich peptides: An abundant source of membrane-permeable peptides having potential as carriers for intracellular protein delivery, J. Biol. Chem. 276 (2001) 5836-5840.
28. O. Harush-Frenkel, N. Debotton, S. Benita, Y. Altschuler, Targeting of nanoparticles to the clathrin-mediated endocytic pathway, Biochem. Biophys. Res. Commun. 353 (2007) 26–32.