Lentivirus-mediated reprogramming of somatic cells in the absence of transgenic transcription factors

Kane, N. M. et al. (2010) Lentivirus-mediated reprogramming of somatic cells in the absence of transgenic transcription factors. Molecular Therapy, 18(12), pp. 2139-2145. (doi:10.1038/mt.2010.231)

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Publisher's URL: http://dx.doi.org/10.1038/mt.2010.231

Abstract

Retroviral vectors remain the most efficient and widely applied system for induction of pluripotency. However, mutagenic effects have been documented in both laboratory and clinical gene therapy studies, principally as a result of dysregulated host gene expression in the proximity of defined integration sites. Here, we report that cells with characteristics of pluripotent stem cells can be produced from normal human fibroblasts in the absence of reprogramming transcription factors (TFs) during lentiviral (LV) vector–mediated gene transfer. This occurred via induced alterations in host gene and microRNA (miRNA) expression and detrimental changes in karyotype. These findings demonstrate that vector-induced genotoxicity may alone play a role in somatic cell reprogramming derivation and urges caution when using integrating vectors in this setting. Clearer understanding of this process may additionally reveal novel insights into reprogramming pathways.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Houslay, Professor Miles and Baker, Professor Andrew and Kane, Dr Nicole and Mountford, Dr Joanne and Milligan, Professor Graeme and Greig, Ms Jenny and Lee, Dr Wai Kwong
Authors: Kane, N. M., Nowrouzi, A., Mukherjee, S., Blundell, M. P., Greig, J. A., Lee, W. K., Houslay, M. D., Milligan, G., Mountford, J. C., von Kalle, C., Schmidt, M., Thrasher, A. J., and Baker, A. H.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Neuroscience and Psychology
Journal Name:Molecular Therapy
Journal Abbr.:Mol. Ther.
ISSN:1525-0016
ISSN (Online):1525-0024
Published Online:26 October 2010
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
487811Induced pluripoptent cells: analysis of cell reprogramming of dermal fibroblasts derived from patients with disease vs age-matched healthy controlsAndrew BakerBritish Heart Foundation (BHF)PG/09/007/26675RI CARDIOVASCULAR & MEDICAL SCIENCES