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Guiding differentiation of stem cells in vivo by tetracycline-controlled expression of key transcription factors
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. (Neuroanatomi)
Unviersity of Erlangen-Nuremberg. (Microbiology)
2012 (English)In: Cell Transplantation, ISSN 0963-6897, E-ISSN 1555-3892, Vol. 21, 2537-2554 p.Article, review/survey (Refereed) Published
Abstract [en]

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 towards 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.

Place, publisher, year, edition, pages
2012. Vol. 21, 2537-2554 p.
Keyword [en]
Cell survival; Central nervous system; Gene regulation
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Research subject
URN: urn:nbn:se:uu:diva-194505DOI: 10.3727/096368911X637407ISI: 000315001400001OAI: diva2:605636
Available from: 2013-02-14 Created: 2013-02-14 Last updated: 2013-04-01Bibliographically approved

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Kozlova, Elena
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