Assessment of the effects of virus-mediated limited Oct4 overexpression on the structure of the hippocampus and behavior in mice
1
조회
0
다운로드
2
인용
0
참고문헌
키워드
초록
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. [BMB reports 2011; 44(12): 793-798]
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. [BMB reports 2011; 44(12): 793-798]
참고문헌 (25)
- Ryan, A. K, "POU domain family values: flexibility, partnerships, and developmental codes", Genes Dev, 11, pp.1207~ (1997)
- Okamoto, K, "A novel octamer binding transcription factor is differentially expressed in mouse embryonic cells", Cell, 60, pp.461~472 (1990)
- Rosner, M. H, "A POUdomain transcription factor in early stem cells and germ cells of the mammalian embryo", Nature, 345, pp.686~692 (1990)
- Pesce, M, "Oct 4: gatekeeper in the beginnings of mammalian development", Stem Cells, 19, pp.271~278 (2001)
- Hochedlinger, K, "Ectopic expression of Oct-4 blocks progenitor-cell differentiation and causes dysplasia in epithelial tissues", Cell, 121, pp.465~477 (2005)
- Niwa, H, "Quantitative expression of Oct-3", 4 defines differentiation, dedifferentiation or self-renewal of ES cells, 2000, pp.24, 372~376
- Nichols, J, "Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4", Cell, 95, pp.379~391 (1998)
- Takahashi, K, "Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors", Cell, 126, pp.663~676 (2006)
- Takahashi, K, "Induction of pluripotent stem cells from adult human fibroblasts by defined factors", Cell, 131, pp.861~872 (2007)
- Meissner, A, "Direct reprogramming of genetically unmodified fibroblasts into pluripotent stem cells", Nat. Biotechnol, 25, pp.1177~1181 (2007)
- Okita, K, "Generation of germline-competent induced pluripotent stem cells", Nature, 448, pp.313~317 (2007)
- Lowry, W, "Generation of human induced pluripotent stem cells from dermal fibroblasts", Proc. Natl. Acad. Sci, 105, pp.2883~ (2008)
- Park, I. H., "Reprogramming of human somatic cells to pluripotency with defined factors", Nature, 451, pp.141~146 (2007)
- Kim, J. B, "Direct reprogramming of human neural stem cells by OCT4", NATURE, 461, pp.649~U93 (2009), NATURE PUBLISHING GROUP
- Kim, J. B, "Oct4-Induced Pluripotency in Adult Neural Stem Cells", CELL, 136(3), pp.411~419, CELL PRESS
- Akamatsu, W, "Suppression of Oct4 by germ cell nuclear factor restricts pluripotency and promotes neural stem cell development in the early neural lineage", J. Neurosci, 29, pp.2113~ (2009)
- Belzung, C, "Measuring normal and pathological anxiety-like behaviour in mice: a review", Behav. Brain Res, 125, pp.141~149 (2001)
- Ko, H. G, "Effect of ablated hippocampal neurogenesis on the formation and extinction of contextual fear memory", Mol. Brain, 2(1) (2009), BioMed Central
- Pellow, S, "Validation of open: closed arm entries in an elevated plus-maze as a measure of anxiety in the rat", J. Neurosci. Meth, 14, pp.149~167 (1985)
- Kanai, M, "Tryptophan 2,3-dioxygenase is a key modulator of physiological neurogenesis and anxiety-related behavior in mice", Mol. Brain, 2, pp.8~ (2009)
- Walf, A. A, "The use of the elevated plus maze as an assay of anxiety-related behavior in rodents", Nat. Protoc, 2, pp.322~328 (2007)
- Bertholet, J. Y, "Spatial and non-spatial spontaneous alternation and hippocampal mossy fibre distribution in nine inbred mouse strains", Behav. Brain Res, 43, pp.197~202 (1991)
- Phillips, R, "Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning", Behav. Neurosci, 106, pp.274~ (1992)
- Sahay, A, "Increasing adult hippocampal neurogenesis is sufficient to improve pattern separation", Nature, 472, pp.466~470 (2011)
- 박수원, "Aged wild-type littermates and APPswe+PS1", △E9 mice present similar deficits in associative learning and spatial memory independent of amyloid load, 2010, pp.32(1), 63~70[DOI]
