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The ROSA26-iPSC mouse: a conditional, inducible, and exchangeable resource for studying cellular (De)differentiation.
Haenebalcke, Lieven Goossens, Steven Dierickx, Pieterjan Bartunkova, Sonia D'Hont, Jinke Haigh, Katharina Hochepied, Tino Wirth, Dagmar Nagy, Andras Haigh, Jody J
Haenebalcke, Lieven
Goossens, Steven
Dierickx, Pieterjan
Bartunkova, Sonia
D'Hont, Jinke
Haigh, Katharina
Hochepied, Tino
Wirth, Dagmar
Nagy, Andras
Haigh, Jody J
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2013-02-21
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Abstract
Control of cellular (de)differentiation in a temporal, cell-specific, and exchangeable manner is of paramount importance in the field of reprogramming. Here, we have generated and characterized a mouse strain that allows iPSC generation through the Cre/loxP conditional and doxycycline/rtTA-controlled inducible expression of the OSKM reprogramming factors entirely from within the ROSA26 locus. After reprogramming, these factors can be replaced by genes of interest-for example, to enhance lineage-directed differentiation-with the use of a trap-coupled RMCE reaction. We show that, similar to ESCs, Dox-controlled expression of the cardiac transcriptional regulator Mesp1 together with Wnt inhibition enhances the generation of functional cardiomyocytes upon in vitro differentiation of such RMCE-retargeted iPSCs. This ROSA26-iPSC mouse model is therefore an excellent tool for studying both cellular reprogramming and lineage-directed differentiation factors from the same locus and will greatly facilitate the identification and ease of functional characterization of the genetic/epigenetic determinants involved in these complex processes.
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The ROSA26-iPSC mouse: a conditional, inducible, and exchangeable resource for studying cellular (De)differentiation. 2013, 3 (2):335-41 Cell Rep
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en
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2211-1247
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