title: Guiding differentiation of stem cells in vivo by tetracycline-controlled expression of key transcription factors.
abstract: Transplantation of stem or progenitor cells is an attractive strategy for cell replacement therapy. However, poor long-term survival and insufficiently reproducible differentiation to functionally appropriate cells in vivo still present major obstacles for translation of this methodology  to clinical applications. Numerous experimental studies have revealed that the expression of just a few transcription factors can be sufficient to drive stem cell differentiation toward a specific cell type, to transdifferentiate cells from one fate to another, or to dedifferentiate mature  cells to pluripotent stem/progenitor cells (iPSCs). We thus propose here to apply the strategy of expressing the relevant key transcription factors to guide the differentiation of transplanted cells to the desired cell fate in vivo. To achieve this requires tools allowing us to control the  expression of these genes in the transplant. Here, we describe drug-inducible systems that allow us to sequentially and timely activate gene expression from the outside, with a particular emphasis on the Tet system, which has been widely and successfully used in stem cells. These regulatory  systems offer a tool for strictly limiting gene expression to the respective optimal stage after transplantation. This approach will direct the differentiation of the immature stem/progenitor cells in vivo to the desired cell type.
authors.affiliation: Department of Neuroscience, Uppsala University, Uppsala, Sweden. elena.kozlova@neuro.uu.se
authors.forename: Elena N
authors.initials: EN
authors.lastname: Kozlova
authors.forename: Christian
authors.initials: C
authors.lastname: Berens
mesh_terms: D002454:Cell Differentiation; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D013752:Tetracycline / Q000494:pharmacology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D011500:Protein Synthesis Inhibitors; D014157:Transcription Factors; D013752:Tetracycline