Induced pluripotency with endogenous and inducible genes
- Department of Molecular Cell Biology and Regenerative Medicine Program, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden (Netherlands)
- Department of Cell and Molecular Biology, Karolinska Institute, Box 285, S171 77, Stockholm (Sweden)
The recent discovery that two partly overlapping sets of four genes induce nuclear reprogramming of mouse and even human cells has opened up new possibilities for cell replacement therapies. Although the combination of genes that induce pluripotency differs to some extent, Oct4 and Sox2 appear to be a prerequisite. The introduction of four genes, several of which been linked with cancer, using retroviral approaches is however unlikely to be suitable for future clinical applications. Towards developing a safer reprogramming protocol, we investigated whether cell types that express one of the most critical reprogramming genes endogenously are predisposed to reprogramming. We show here that three of the original four pluripotency transcription factors (Oct4, Klf4 and c-Myc or MYCER{sup TAM}) induced reprogramming of mouse neural stem (NS) cells exploiting endogenous SoxB1 protein levels in these cells. The reprogrammed neural stem cells differentiated into cells of each germ layer in vitro and in vivo, and contributed to mouse development in vivo. Thus a combinatorial approach taking advantage of endogenously expressed genes and inducible transgenes may contribute to the development of improved reprogramming protocols.
- OSTI ID:
- 21176133
- Journal Information:
- Experimental Cell Research, Vol. 314, Issue 17; Other Information: DOI: 10.1016/j.yexcr.2008.06.024; PII: S0014-4827(08)00253-X; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0014-4827
- Country of Publication:
- United States
- Language:
- English
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