Induced pluripotency with endogenous and inducible genes

Journal Article · Wed Oct 15 04:00:00 EDT 2008 · Experimental Cell Research

DOI:https://doi.org/10.1016/j.yexcr.2008.06.024· OSTI ID:21176133

Duinsbergen, Dirk ^[1]; Eriksson, Malin ^[2]; Frisen, Jonas ^[2]; Mikkers, Harald ^[1]

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1. Department of Molecular Cell Biology and Regenerative Medicine Program, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden (Netherlands)
2. 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, Journal Name: Experimental Cell Research Journal Issue: 17 Vol. 314; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
GENES
IN VITRO
IN VIVO
MICE
NEOPLASMS
STEM CELLS
THERAPY
TRANSCRIPTION FACTORS