Data set for comparison of cellular dynamics between human AAVS1 locus-modified and wild-type cells

Mizutani, Takeomi; Haga, Hisashi; Kawabata, Kazushige

doi:10.1016/j.dib.2015.12.053

Cited by 3 publications

(3 citation statements)

References 6 publications

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“…The mean-squared displacement (MSD) is a useful measure to find cell persistence of migration in two and three dimension microenvironments [49][50][51][52]. This is calculated as MSD(t) = − → r M (t) − − → r M (0) 2 , where .…”

Section: Mean-squared Displacementmentioning

confidence: 99%

Modeling Active Cell Movement With the Potts Model

2018

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In the last decade, the cellular Potts model has been extensively used to model interacting cell systems at the tissue-level. However, in early applications of this model, cell movement was taken as a consequence of membrane fluctuations due to cell-cell interactions, or as a response to an external chemotactic gradient. Recent findings have shown that eukaryotic cells can exhibit persistent displacements across scales larger than cell size, even in the absence of external signals. Persistent cell motion has been incorporated to the cellular Potts model by many authors in the context of collective motion, chemotaxis and morphogenesis. In this paper, we use the cellular Potts model in combination with a random field applied over each cell. This field promotes a uniform cell motion in a given direction during a certain time interval, after which the movement direction changes. The dynamics of the direction is coupled to a first order autoregressive process. We investigated statistical properties, such as the mean-squared displacement and spatio-temporal correlations, associated to these self-propelled in silico cells in different conditions. The proposed model emulates many properties observed in different experimental setups. By studying low and high density cultures, we find that cell-cell interactions decrease the effective persistent time.

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Section: Mean-squared Displacementmentioning

confidence: 99%

Modeling Active Cell Movement With the Potts Model

2018

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“…The AAVS1 locus has been defined as a bona-fide safe harbor locus in humans 34 , in which an exogenous gene could be efficiently expressed in various cell lines and iPSCs [28][29][30][31][32][33][34][48][49][50][51][52] . Therefore, in this work, we have decided to carry out a targeted integration strategy into the mouse Mbs85 orthologous locus in order to asses if the corresponding mouse locus may serve as a new site where gene editing can be performed in mouse disease models such as Fanconi anemia (FA).…”

Section: Discussionmentioning

confidence: 99%

TALEN mediated gene editing in a mouse model of Fanconi anemia

Pino-Barrio

Giménez

Villanueva

et al. 2020

Sci Rep

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the promising ability to genetically modify hematopoietic stem and progenitor cells by precise gene editing remains challenging due to their sensitivity to in vitro manipulations and poor efficiencies of homologous recombination. This study represents the first evidence of implementing a gene editing strategy in a murine safe harbor locus site that phenotypically corrects primary cells from a mouse model of Fanconi anemia A. By means of the co-delivery of transcription activator-like effector nucleases and a donor therapeutic fAncA template to the Mbs85 locus, we achieved efficient gene targeting (23%) in mFA-A fibroblasts. This resulted in the phenotypic correction of these cells, as revealed by the reduced sensitivity of these cells to mitomycin C. Moreover, robust evidence of targeted integration was observed in murine wild type and FA-A hematopoietic progenitor cells, reaching mean targeted integration values of 21% and 16% respectively, that were associated with the phenotypic correction of these cells. Overall, our results demonstrate the feasibility of implementing a therapeutic targeted integration strategy into the mMbs85 locus, ortholog to the well-validated hAAVS1, constituting the first study of gene editing in mHSC with TALEN, that sets the basis for the use of a new safe harbor locus in mice.

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“…The AAVS1 locus has been defined as a bona-fide safe harbor locus in humans (Lombardo et al, 2011), in which an exogenous gene could be efficiently expressed in various cell lines and iPSCs (DeKelver et al, 2010;Dreyer et al, 2015;Hockemeyer et al, 2009;Li et al, 2017;Lombardo et al, 2011;Mizutani et al, 2016;Mizutani et al, 2015;Oceguera-Yanez et al;Ordovas et al, 2015;Ramachandra et al, 2011;Smith et al, 2008;Zou et al, 2011). Therefore, in this work, we have decided to carry out a targeted integration strategy in the mouse Mbs85 orthologous locus in order to asses if the corresponding mouse locus may serve as a new site where gene editing can be performed in mouse disease models such as Fanconi anemia (FA).…”

Section: Discussionmentioning

confidence: 99%

Therapeutic gene editing in hematopoietic progenitor cells from a mouse model of Fanconi anemia

Pino-Barrio

Giménez

Villanueva

et al. 2018

Preprint

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The promising ability to genetically modify hematopoietic stem and progenitor cells (HSPCs) by precise gene editing remains challenging due to their sensitivity and poor permissiveness. This represents the first evidence of implementing a gene editing strategy in a murine safe harbor locus that phenotypically corrects primary cells derived from a mouse model of Fanconi anemia (FA).By co-delivering TALENs and a donor therapeutic FANCA cassette template to the Mbs85 locus (ortholog of the hAAVS1 safe harbor locus), we achieved efficient gene targeting (23%) in FA mouse embryonic fibroblasts (MEFs). This resulted in the phenotypic correction of these cells, as revealed by the improvement of their hypersensitivity to mitomycinC. Moreover, robust evidence of targeted integration was observed in murine WT and FA-A hematopoietic progenitor cells (HPC) reaching mean targeted integration values of 20.98% and 16.33% respectively, with phenotypic correction of FA HPCs. Overall, our results demonstrate the feasibility of implementing a therapeutic targeted integration strategy in a murine safe harbor locus, such as the Mbs85 gene, of MEFs and murine HPC from a FA mouse model. Supplementary Table 3. Primers and probes used in this study. Forward and reverse primers as well as probes, their sequence, their melting temperature (Tm) and the product size is indicated. In the case of probes, the fluorochrome to which each probe was conjugated is also indicated.

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Data set for comparison of cellular dynamics between human AAVS1 locus-modified and wild-type cells

Cited by 3 publications

References 6 publications

Modeling Active Cell Movement With the Potts Model

Modeling Active Cell Movement With the Potts Model

TALEN mediated gene editing in a mouse model of Fanconi anemia

Therapeutic gene editing in hematopoietic progenitor cells from a mouse model of Fanconi anemia

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