Retrovirus vectors designed for efficient transduction of cytotoxic or cytostatic genes

Ui, Michio; Takada, Misato; Arai, Tohru; Matsumoto, Kazu; Yamada, Koichi; Nakahata, Tatsutoshi; Nishiwaki, Takeshi; Furukawa, Yoichi; Tokino, Takashi; Nakamura, Yusuke; Iba, Hideo

doi:10.1038/sj.gt.3301009

Cited by 11 publications

(8 citation statements)

References 30 publications

(27 reference statements)

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“…The pmU6 derivatives shCre#4 38 , shBrm#4 39 , shDPF1-CDS#1 16 and shDPF3a-3′UTR#2 16 were previously described. These pmU6-based plasmids were doubly digested with BamHI and EcoRI, and inserted into the same sites of pSSSP 40 , pSSCG 35 (EV-1) or pLE-IG (EV-2).…”

Section: Methodsmentioning

confidence: 99%

The role of the SWI/SNF chromatin remodeling complex in maintaining the stemness of glioma initiating cells

Hiramatsu

Kobayashi

et al. 2017

Sci Rep

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Glioma initiating cells (GICs) are thought to contribute to therapeutic resistance and tumor recurrence in glioblastoma, a lethal primary brain tumor in adults. Although the stem-like properties of GICs, such as self-renewal and tumorigenicity, are epigenetically regulated, the role of a major chromatin remodeling complex in human, the SWI/SNF complex, remains unknown in these cells. We here demonstrate that the SWI/SNF core complex, that is associated with a unique corepressor complex through the d4-family proteins, DPF1 or DPF3a, plays essential roles in stemness maintenance in GICs. The seruminduced differentiation of GICs downregulated the endogenous expression of DPF1 and DPF3a, and the shRNA-mediated knockdown of each gene reduced both sphere-forming ability and tumor-forming activity in a mouse xenograft model. Rescue experiments revealed that DPF1 has dominant effects over DPF3a. Notably, whereas we have previously reported that d4-family members can function as adaptor proteins between the SWI/SNF complex and NF-κB dimers, this does not significantly contribute to maintaining the stemness properties of GICs. Instead, these proteins were found to link a corepressor complex containing the nuclear receptor, TLX, and LSD1/RCOR2 with the SWI/SNF core complex. Collectively, our results indicate that DPF1 and DPF3a are potential therapeutic targets for glioblastoma.Glioblastoma multiforme (GBM) is the most common malignant brain tumor in adults and remains incurable in spite of aggressive treatment approaches. A large body of evidence now indicates that stem-like cells, designated as glioma initiating cells (GICs), are thought to drive GBM propagation and cause therapeutic resistance in these tumors 1-3 . Chromatin structure modification has been shown to be an important determinant of GIC stemness maintenance as well as the induction of their differentiation 4,5 . Recently, using gene expression data from both stem-like and differentiated cell populations, it was shown that the simultaneous expression of four core transcription factors, POU3F2, SALL2, SOX2 and OLIG2, can reprogram differentiated GBM cells into spherogenic stem-like tumor-propagating cells 6 . These results demonstrate a plastic developmental hierarchy in GBM cell populations and reveal essential roles of epigenetic regulation in these biological processes 7 . In humans, the ATP-dependent chromatin remodeling factor, SWI/SNF complex, has been reported to play essential epigenetic roles in many biological processes [8][9][10] . As the catalytic subunit, each SWI/SNF complex has a single molecule of either BRG1 or Brm, but not both. The molecular components of these SWI/SNF complexes are now known to be highly polymorphic, in which some subunits that are encoded by homologous gene family members are integrated into the specific position of the complex in a mutually exclusive manner 8, 9, 11 . Importantly, exchange of a subunit with another family member has often been observed during several developmental processes within either the SWI/SNF core...

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Section: Methodsmentioning

confidence: 99%

The role of the SWI/SNF chromatin remodeling complex in maintaining the stemness of glioma initiating cells

Hiramatsu

Kobayashi

et al. 2017

Sci Rep

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“…These sequences not only can inhibit the growth of transduced cells, but in the case of retroviral vectors, they can also inhibit the production of packaging cell lines. 27 The advantage of an inducible promoter is indeed dramatized when one wishes to express a tumor suppressor gene product, as shown in our experiments described above. When we used the 486/FLAG construct with the noninducible promoter, we obtained several antibiotic-resistant clones, but the expression of 486/FLAG was not detectable.…”

Section: Discussionmentioning

confidence: 80%

Efficient in vitro and in vivo gene regulation of a retrovirally delivered pro-apoptotic factor under the control of the Drosophila HSP70 promoter

Romano

Reiss

et al. 2001

Gene Ther

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We have developed a self-inactivating retroviral vector system with an internal, inducible Drosophila HSP70 promoter. This vector system delivers the desired transgene into cells rapidly and efficiently. It generates mixed populations of transduced cells where the transgene is inducible, and does not require the isolation of specific clones. Since the transgene is not expressed (or poorly expressed) at the restrictive

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“…This titer corresponds to 40 infectious viral particles per cell under our conditions. Since VSV-G pseudotyped retroviral vectors can be concentrated by ultracentrifugation, they have excellent transduction efficiencies as shown here and in other applications for transgenic animals and gene therapy (13,22). and GFP expression in cultured embryonic fibroblasts obtained from 10-day stage G 1 transgenic quail embryos.…”

Section: Discussionmentioning

confidence: 86%

Production of Transgenic Quails with High Frequency of Germ-Line Transmission Using VSV-G Pseudotyped Retroviral Vector

Mizuarai

Ono

Yamaguchi

et al. 2001

Biochemical and Biophysical Research Communications

111

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Retrovirus vectors designed for efficient transduction of cytotoxic or cytostatic genes

Cited by 11 publications

References 30 publications

The role of the SWI/SNF chromatin remodeling complex in maintaining the stemness of glioma initiating cells

The role of the SWI/SNF chromatin remodeling complex in maintaining the stemness of glioma initiating cells

Efficient in vitro and in vivo gene regulation of a retrovirally delivered pro-apoptotic factor under the control of the Drosophila HSP70 promoter

Production of Transgenic Quails with High Frequency of Germ-Line Transmission Using VSV-G Pseudotyped Retroviral Vector

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