| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2042176 | Cell Reports | 2013 | 7 Pages |
SummaryControl 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.
Graphical AbstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Conditional and inducible reprogrammable mouse model presented ► Allows removal of the Yamanaka factors after reprogramming ► Fully and partially reprogrammed endothelial cells generated ► Lineage-directed differentiation of iPSCs toward beating cardiomyocytes
