title: The ROSA26-iPSC mouse: a conditional, inducible, and exchangeable resource for studying cellular (De)differentiation.
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.
authors: Vascular Cell Biology Unit, VIB Department for Molecular Biomedical Research, Ghent University, Technologiepark 927, 9052 Zwijnaarde Ghent, Belgium.
authors: Lieven
authors: L
authors: Haenebalcke
authors: Steven
authors: S
authors: Goossens
authors: Pieterjan
authors: P
authors: Dierickx
authors: Sonia
authors: S
authors: Bartunkova
authors: Jinke
authors: J
authors: D'Hont
authors: Katharina
authors: K
authors: Haigh
authors: Tino
authors: T
authors: Hochepied
authors: Dagmar
authors: D
authors: Wirth
authors: Andras
authors: A
authors: Nagy
authors: Jody J
authors: JJ
authors: Haigh
mesh_terms: D000483:Alleles; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage; D002478:Cells, Cultured; D065150:Cellular Reprogramming; D004318:Doxycycline / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D056426:Genetic Loci; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D032383:Myocytes, Cardiac / Q000166:cytology; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D022661:RNA, Untranslated; D051153:Wnt Proteins / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004318:Doxycycline; D011506:Proteins; D022661:RNA, Untranslated; D051153:Wnt Proteins; C110853:Gt(ROSA)26Sor non-coding RNA, mouse; C101538:Mesp1 protein, mouse