Pluripotent stem cells induced from adult neural stem cells by reprogramming with two factors

• Published in: Nature 2008-07, Vol.454 (7204), p.646-650
• Main Authors: Schöler, Hans R, Kim, Jeong Beom, Zaehres, Holm, Wu, Guangming, Gentile, Luca, Ko, Kinarm, Sebastiano, Vittorio, Araúzo-Bravo, Marcos J, Ruau, David, Han, Dong Wook, Zenke, Martin
• Format: Article
• Language: English
• Subjects: Adult Stem Cells - cytology; Adult Stem Cells - metabolism; Animals; Biological and medical sciences; Cell Differentiation - genetics; Cells, Cultured; Cellular Reprogramming; Chemical compounds; Chimera; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; E coli; Female; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Profiling; General aspects. Models. Methods; Genes, myc - genetics; HMGB Proteins - genetics; HMGB Proteins - metabolism; Homeodomain Proteins - genetics; Humanities and Social Sciences; Kruppel-Like Transcription Factors - genetics; Kruppel-Like Transcription Factors - metabolism; letter; Male; Mice; Mice, Nude; Mice, Transgenic; multidisciplinary; Neurons - cytology; Octamer Transcription Factor-3 - genetics; Octamer Transcription Factor-3 - metabolism; Offspring; Physiological aspects; Pluripotent Stem Cells - cytology; Pluripotent Stem Cells - metabolism; Proteins - genetics; Proto-Oncogene Proteins c-myc - metabolism; Retrovirus; RNA, Untranslated; Science; Science (multidisciplinary); Signal transduction; Somatic cells; SOXB1 Transcription Factors; Stem cells; Transcription Factors - genetics; Transcription Factors - metabolism; Transduction, Genetic; Vertebrates: nervous system and sense organs
• ISSN: 0028-0836; 1476-4687; 1476-4679
• DOI: 10.1038/nature07061

Reprogramming of somatic cells is a valuable tool to understand the mechanisms of regaining pluripotency and further opens up the possibility of generating patient-specific pluripotent stem cells. Reprogramming of mouse and human somatic cells into pluripotent stem cells, designated as induced pluripotent stem (iPS) cells, has been possible with the expression of the transcription factor quartet Oct4 (also known as Pou5f1), Sox2, c-Myc and Klf4 (refs 1-11). Considering that ectopic expression of c-Myc causes tumorigenicity in offspring and that retroviruses themselves can cause insertional mutagenesis, the generation of iPS cells with a minimal number of factors may hasten the clinical application of this approach. Here we show that adult mouse neural stem cells express higher endogenous levels of Sox2 and c-Myc than embryonic stem cells, and that exogenous Oct4 together with either Klf4 or c-Myc is sufficient to generate iPS cells from neural stem cells. These two-factor iPS cells are similar to embryonic stem cells at the molecular level, contribute to development of the germ line, and form chimaeras. We propose that, in inducing pluripotency, the number of reprogramming factors can be reduced when using somatic cells that endogenously express appropriate levels of complementing factors.