BMB Reports

Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Assessment of the effects of virus-mediated limited Oct4 overexpression on the structure of the hippocampus and behavior in mice

  • Sim, Su-Eon (Brain and Cognitive Sciences, College of Natural Sciences, Seoul National University) ;
  • Park, Soo-Won (National Creative Research Initiative Center for Memory, Departments of Biological Sciences, Seoul National University) ;
  • Choi, Sun-Lim (National Creative Research Initiative Center for Memory, Departments of Biological Sciences, Seoul National University) ;
  • Yu, Nam-Kyung (National Creative Research Initiative Center for Memory, Departments of Biological Sciences, Seoul National University) ;
  • Ko, Hyoung-Gon (National Creative Research Initiative Center for Memory, Departments of Biological Sciences, Seoul National University) ;
  • Jang, Deok-Jin (Department of Applied Biology, College of Ecology and Environment, Kyungpook National University) ;
  • Lee, Kyung-Min (Department of Anatomy, School of Medicine, Brain Science & Engineering Institute, Kyungpook National University) ;
  • Kaang, Bong-Kiun (Brain and Cognitive Sciences, College of Natural Sciences, Seoul National University)
  • Received : 2011.08.25
  • Accepted : 2011.09.26
  • Published : 2011.12.31
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Abstract

Recently, pluripotency induction or cellular reprogramming by introducing critical transcription factors has been extensively studied, but has been demonstrated only in vitro. Based on reports that Oct4 is critically involved in transforming neural stem cells into pluripotent cells, we used the lentiviral vector to introduce the Oct4 gene into the hippocampal dentate gyrus (DG) of adult mice. We examined whether this manipulation led to cellular or behavioral changes, possibly through processes involving the transformation of NS cells into pluripotent cells. The Oct4 lentivirus-infused group and the green fluorescent protein lentivirus-infused group showed a similar thickness of the DG and a comparable level of synaptophysin expression in the DG. Furthermore, our behavioral analyses did not show any differences between the groups concerning exploratory activity, anxiety, or memory abilities. This first trial for pluripotency induction in vivo, despite negative results, provides implications and information for future studies on in vivo cellular reprogramming.

Keywords

References

  1. Ryan, A. K. and Rosenfeld, M. G. (1997) POU domain family values: flexibility, partnerships, and developmental codes. Genes Dev. 11, 1207. https://doi.org/10.1101/gad.11.10.1207
  2. Okamoto, K., Okazawa, H., Okuda, A., Sakai, M., Muramatsu, M. and Hamada, H. (1990) A novel octamer binding transcription factor is differentially expressed in mouse embryonic cells. Cell 60, 461-472. https://doi.org/10.1016/0092-8674(90)90597-8
  3. Rosner, M. H., Vigano, M. A., Ozato, K., Timmons, P. M., Poirie, F., Rigby, P. W. J. and Staudt, L. M. (1990) A POU-domain transcription factor in early stem cells and germ cells of the mammalian embryo. Nature 345, 686-692. https://doi.org/10.1038/345686a0
  4. Pesce, M. and Scholer, H. R. (2001) Oct 4: gatekeeper in the beginnings of mammalian development. Stem Cells 19, 271-278. https://doi.org/10.1634/stemcells.19-4-271
  5. Hochedlinger, K., Yamada, Y., Beard, C. and Jaenisch, R. (2005) Ectopic expression of Oct-4 blocks progenitor-cell differentiation and causes dysplasia in epithelial tissues. Cell 121, 465-477. https://doi.org/10.1016/j.cell.2005.02.018
  6. Niwa, H., Miyazaki, J. and Smith, A. G. (2000) Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells. Nat. Genet. 24, 372-376. https://doi.org/10.1038/74199
  7. Nichols, J., Zevnik, B., Anastassiadis, K., Niwa, H., Klewe-Nebenius, D., Chambers, I., Scholer, H. and Smith, A. (1998) Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4. Cell 95, 379-391. https://doi.org/10.1016/S0092-8674(00)81769-9
  8. 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. https://doi.org/10.1016/j.cell.2006.07.024
  9. Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K. and Yamanaka, S. (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131, 861-872. https://doi.org/10.1016/j.cell.2007.11.019
  10. Meissner, A., Wernig, M. and Jaenisch, R. (2007) Direct reprogramming of genetically unmodified fibroblasts into pluripotent stem cells. Nat. Biotechnol. 25, 1177-1181. https://doi.org/10.1038/nbt1335
  11. Okita, K., Ichisaka, T. and Yamanaka, S. (2007) Generation of germline-competent induced pluripotent stem cells. Nature 448, 313-317. https://doi.org/10.1038/nature05934
  12. Lowry, W., Richter, L., Yachechko, R., Pyle, A., Tchieu, J., Sridharan, R., Clark, A. and Plath, K. (2008) Generation of human induced pluripotent stem cells from dermal fibroblasts. Proc. Natl. Acad. Sci. 105, 2883. https://doi.org/10.1073/pnas.0711983105
  13. Park, I. H., Zhao, R., West, J. A., Yabuuchi, A., Huo, H., Ince, T. A., Lerou, P. H., Lensch, M. W. and Daley, G. Q. (2007) Reprogramming of human somatic cells to pluripotency with defined factors. Nature 451, 141-146.
  14. Kim, J. B., Greber, B., Arauzo-Bravo, M. J., Meyer, J., Park, K. I., Zaehres, H. and Scholer, H. R. (2009) Direct reprogramming of human neural stem cells by OCT4. Nature 461, 649-643. https://doi.org/10.1038/nature08436
  15. Kim, J. B., Sebastiano, V., Wu, G., Arauzo-Bravo, M. J., Sasse, P., Gentile, L., Ko, K., Ruau, D., Ehrich, M. and van den Boom, D. (2009) Oct4-induced pluripotency in adult neural stem cells. Cell 136, 411-419. https://doi.org/10.1016/j.cell.2009.01.023
  16. Akamatsu, W., DeVeale, B., Okano, H., Cooney, A. J. and van der Kooy, D. (2009) Suppression of Oct4 by germ cell nuclear factor restricts pluripotency and promotes neural stem cell development in the early neural lineage. J. Neurosci. 29, 2113. https://doi.org/10.1523/JNEUROSCI.4527-08.2009
  17. Belzung, C. and Griebel, G. (2001) Measuring normal and pathological anxiety-like behaviour in mice: a review. Behav. Brain Res. 125, 141-149. https://doi.org/10.1016/S0166-4328(01)00291-1
  18. Ko, H. G., Jang, D. J., Son, J., Kwak, C., Choi, J. H., Ji, Y. H., Lee, Y. S., Son, H. and Kaang, B. K. (2009) Effect of ablated hippocampal neurogenesis on the formation and extinction of contextual fear memory. Mol Brain 2, 1. https://doi.org/10.1186/1756-6606-2-1
  19. Pellow, S., Chopin, P., File, S. E. and Briley, M. (1985) Validation of open: closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. J. Neurosci. Meth. 14, 149-167. https://doi.org/10.1016/0165-0270(85)90031-7
  20. Kanai, M., Funakoshi, H., Takahashi, H., Hayakawa, T., Mizuno, S., Matsumoto, K. and Nakamura, T. (2009) Tryptophan 2,3-dioxygenase is a key modulator of physiological neurogenesis and anxiety-related behavior in mice. Mol. Brain 2, 8. https://doi.org/10.1186/1756-6606-2-8
  21. Walf, A. A. and Frye, C. A. (2007) The use of the elevated plus maze as an assay of anxiety-related behavior in rodents. Nat. Protoc. 2, 322-328. https://doi.org/10.1038/nprot.2007.44
  22. Bertholet, J. Y. and Crusio, W. E. (1991) Spatial and non-spatial spontaneous alternation and hippocampal mossy fibre distribution in nine inbred mouse strains. Behav. Brain Res. 43, 197-202. https://doi.org/10.1016/S0166-4328(05)80071-3
  23. Phillips, R. and LeDoux, J. (1992) Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning. Behav. Neurosci. 106, 274. https://doi.org/10.1037/0735-7044.106.2.274
  24. Sahay, A., Scobie, K. N., Hill, A. S., O'Carroll, C. M., Kheirbek, M. A., Burghardt, N. S., Fenton, A. A., Dranovsky, A. and Hen, R. (2011) Increasing adult hippocampal neurogenesis is sufficient to improve pattern separation. Nature 472, 466-470. https://doi.org/10.1038/nature09817
  25. Park, S. W., Ko, H. G., Lee, N., Lee, H. R., Rim, Y. S., Kim, H., Lee, K. M. and Kaang, B. K. (2010) Aged wild-type littermates and APPswe+ PS1/¥ÄE9 mice present similar deficits in associative learning and spatial memory independent of amyloid load. Genes & Genomics 32, 63-70. https://doi.org/10.1007/s13258-010-0833-8

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