International Journal of Stem Cells

Korean Society for Stem Cell Research (한국줄기세포학회)
권호 표지
DOI QR코드

DOI QR Code

Inhibition of Class I Histone Deacetylase Enhances Self-Reprogramming of Spermatogonial Stem Cells into Pluripotent Stem Cells

  • Yukyeong Lee (Department of Stem Cell Biology, Konkuk University School of Medicine) ;
  • Seung-Won Lee (Department of Stem Cell Biology, Konkuk University School of Medicine) ;
  • Dahee Jeong (Department of Stem Cell Biology, Konkuk University School of Medicine) ;
  • Hye Jeong Lee (Department of Stem Cell Biology, Konkuk University School of Medicine) ;
  • Na Young Choi (Department of Stem Cell Biology, Konkuk University School of Medicine) ;
  • Jin Seok Bang (Department of Stem Cell Biology, Konkuk University School of Medicine) ;
  • Seokbeom Ham (Department of Stem Cell Biology, Konkuk University School of Medicine) ;
  • Kinarm, Ko (Department of Stem Cell Biology, Konkuk University School of Medicine)
  • Received : 2022.07.05
  • Accepted : 2022.09.21
  • Published : 2023.02.28
Download PDF
⟨ Previous Next ⟩

Abstract

Background and Objectives: Spermatogonial stem cells (SSCs) are the most primitive cells in spermatogenesis and are the only adult stem cells capable of passing on the genome of a given species to the next generation. SSCs are the only adult stem cells known to exhibit high Oct4 expression and can be induced to self-reprogram into pluripotent cells depending on culture conditions. Epigenetic modulation is well known to be involved in the induction of pluripotency of somatic cells. However, epigenetic modulation in self-reprogramming of SSCs into pluripotent cells has not been studied. Methods and Results: In this study, we examined the involvement of epigenetic modulation by assessing whether selfreprogramming of SSCs is enhanced by treatment with epigenetic modulators. We found that second-generation selective class I HDAC inhibitors increased SSC reprogramming efficiency, whereas non-selective HDAC inhibitors had no effect. Conclusions: We showed that pluripotent stem cells derived from adult SSCs by treatment with small molecules with epigenetic modulator functions exhibit pluripotency in vitro and in vivo. Our results suggest that the mechanism of SSC reprogramming by epigenetic modulator can be used for important applications in epigenetic reprogramming research.

Keywords

Acknowledgement

This study was supported by Konkuk University in 2021.

References

  1. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006;126:663-676
  2. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 2007;131:861-872
  3. Bernstein BE, Meissner A, Lander ES. The mammalian epigenome. Cell 2007;128:669-681
  4. Cedar H, Bergman Y. Linking DNA methylation and histone modification: patterns and paradigms. Nat Rev Genet 2009;10:295-304
  5. Mikkelsen TS, Hanna J, Zhang X, Ku M, Wernig M, Schorderet P, Bernstein BE, Jaenisch R, Lander ES, Meissner A. Dissecting direct reprogramming through integrative genomic analysis. Nature 2008;454:49-55 Erratum in: Nature 2008;454:794
  6. Tegelenbosch RA, de Rooij DG. A quantitative study of spermatogonial multiplication and stem cell renewal in the C3H/101 F1 hybrid mouse. Mutat Res 1993;290:193-200
  7. Dann CT, Alvarado AL, Molyneux LA, Denard BS, Garbers DL, Porteus MH. Spermatogonial stem cell self-renewal requires OCT4, a factor downregulated during retinoic acidinduced differentiation. Stem Cells 2008;26:2928-2937
  8. Kanatsu-Shinohara M, Morimoto T, Toyokuni S, Shinohara T. Regulation of mouse spermatogonial stem cell self-renewing division by the pituitary gland. Biol Reprod 2004;70:1731-1737
  9. Ko K, Tapia N, Wu G, Kim JB, Bravo MJ, Sasse P, Glaser T, Ruau D, Han DW, Greber B, Hausdorfer K, Sebastiano V, Stehling M, Fleischmann BK, Brustle O, Zenke M, Scholer HR. Induction of pluripotency in adult unipotent germline stem cells. Cell Stem Cell 2009;5:87-96
  10. Pesce M, Wang X, Wolgemuth DJ, Scholer H. Differential expression of the Oct-4 transcription factor during mouse germ cell differentiation. Mech Dev 1998;71:89-98
  11. Ko K, Arauzo-Bravo MJ, Kim J, Stehling M, Scholer HR. Conversion of adult mouse unipotent germline stem cells into pluripotent stem cells. Nat Protoc 2010;5:921-928
  12. Lee SW, Wu G, Choi NY, Lee HJ, Bang JS, Lee Y, Lee M, Ko K, Scholer HR, Ko K. Self-reprogramming of spermatogonial stem cells into pluripotent stem cells without microenvironment of feeder cells. Mol Cells 2018;41:631-638
  13. Bang JS, Choi NY, Lee M, Ko K, Park YS, Ko K. Reprogramming of cancer cells into induced pluripotent stem cells questioned. Int J Stem Cells 2019;12:430-439
  14. Ko K, Wu G, Arauzo-Bravo MJ, Kim J, Francine J, Greber B, Muhlisch J, Joo JY, Sabour D, Fruhwald MC, Tapia N, Scholer HR. Autologous pluripotent stem cells generated from adult mouse testicular biopsy. Stem Cell Rev Rep 2012;8:435-444
  15. Choi NY, Park YS, Ryu JS, Lee HJ, Arauzo-Bravo MJ, Ko K, Han DW, Scholer HR, Ko K. A novel feeder-free culture system for expansion of mouse spermatogonial stem cells. Mol Cells 2014;37:473-479
  16. Hou P, Li Y, Zhang X, Liu C, Guan J, Li H, Zhao T, Ye J, Yang W, Liu K, Ge J, Xu J, Zhang Q, Zhao Y, Deng H. Pluripotent stem cells induced from mouse somatic cells by small-molecule compounds. Science 2013;341:651-654
  17. Brustle O, Jones KN, Learish RD, Karram K, Choudhary K, Wiestler OD, Duncan ID, McKay RD. Embryonic stem cell-derived glial precursors: a source of myelinating transplants. Science 1999;285:754-756
  18. Igelmund P, Fleischmann BK, Fischer IR, Soest J, Gryshchenko O, Bohm-Pinger MM, Sauer H, Liu Q, Hescheler J. Action potential propagation failures in long-term recordings from embryonic stem cell-derived cardiomyocytes in tissue culture. Pflugers Arch 1999;437:669-679
  19. Lee HJ, Choi NY, Lee SW, Ko K, Hwang TS, Han DW, Lim J, Scholer HR, Ko K. Epigenetic alteration of imprinted genes during neural differentiation of germline-derived pluripotent stem cells. Epigenetics 2016;11:177-183
  20. Kim KP, Han DW, Kim J, Scholer HR. Biological importance of OCT transcription factors in reprogramming and development. Exp Mol Med 2021;53:1018-1028
  21. Federation AJ, Bradner JE, Meissner A. The use of small molecules in somatic-cell reprogramming. Trends Cell Biol 2014;24:179-187
  22. Huangfu D, Maehr R, Guo W, Eijkelenboom A, Snitow M, Chen AE, Melton DA. Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds. Nat Biotechnol 2008;26:795-797
  23. Huangfu D, Osafune K, Maehr R, Guo W, Eijkelenboom A, Chen S, Muhlestein W, Melton DA. Induction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2. Nat Biotechnol 2008;26:1269-1275
  24. Shi Y, Desponts C, Do JT, Hahm HS, Scholer HR, Ding S. Induction of pluripotent stem cells from mouse embryonic fibroblasts by Oct4 and Klf4 with small-molecule compounds. Cell Stem Cell 2008;3:568-574
  25. Zhao Y, Zhao T, Guan J, Zhang X, Fu Y, Ye J, Zhu J, Meng G, Ge J, Yang S, Cheng L, Du Y, Zhao C, Wang T, Su L, Yang W, Deng H. A XEN-like state bridges somatic cells to pluripotency during chemical reprogramming. Cell 2015;163:1678-1691
  26. Staszkiewicz J, Power RA, Harkins LL, Barnes CW, Strickler KL, Rim JS, Bondioli KR, Eilersten KJ. Silencing histone deacetylase-specific isoforms enhances expression of pluripotency genes in bovine fibroblasts. Cell Reprogram 2013;15:397-404
  27. Saha A, Pandian GN, Sato S, Taniguchi J, Hashiya K, Bando T, Sugiyama H. Synthesis and biological evaluation of a targeted DNA-binding transcriptional activator with HDAC8 inhibitory activity. Bioorg Med Chem 2013;21:4201-4209
  28. de Ruijter AJ, van Gennip AH, Caron HN, Kemp S, van Kuilenburg AB. Histone deacetylases (HDACs): characterization of the classical HDAC family. Biochem J 2003;370(Pt 3):737-749
  29. Gregoretti IV, Lee YM, Goodson HV. Molecular evolution of the histone deacetylase family: functional implications of phylogenetic analysis. J Mol Biol 2004;338:17-31
  30. Haberland M, Montgomery RL, Olson EN. The many roles of histone deacetylases in development and physiology: implications for disease and therapy. Nat Rev Genet 2009;10:32-42
  31. Kang J, Shakya A, Tantin D. Stem cells, stress, metabolism and cancer: a drama in two Octs. Trends Biochem Sci 2009;34:491-499
  32. Pan GJ, Chang ZY, Scholer HR, Pei D. Stem cell pluripotency and transcription factor Oct4. Cell Res 2002;12:321-329
  33. Shi G, Jin Y. Role of Oct4 in maintaining and regaining stem cell pluripotency. Stem Cell Res Ther 2010;1:39
  34. Tantin D. Oct transcription factors in development and stem cells: insights and mechanisms. Development 2013;140:2857-2866
  35. Wu G, Scholer HR. Role of Oct4 in the early embryo development. Cell Regen 2014;3:7