Pluripotent stem cells induced from adult neural stem cells by reprogramming with two factors.
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.
Kim
Jeong Beom
JB
Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Röntgenstrasse 20, 48149 Münster, NRW, Germany.
Zaehres
Holm
H
Wu
Guangming
G
Gentile
Luca
L
Ko
Kinarm
K
Sebastiano
Vittorio
V
Araúzo-Bravo
Marcos J
MJ
Ruau
David
D
Han
Dong Wook
DW
Zenke
Martin
M
Schöler
Hans R
HR
D053687:Adult Stem Cells / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D065150:Cellular Reprogramming; D002678:Chimera; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D016259:Genes, myc / Q000235:genetics; D024002:HMGB Proteins / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology*; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism*; D011506:Proteins / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D022661:RNA, Untranslated; D055748:SOXB1 Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014161:Transduction, Genetic
D004268:DNA-Binding Proteins; C110853:Gt(ROSA)26Sor non-coding RNA, mouse; D024002:HMGB Proteins; D018398:Homeodomain Proteins; C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; C489428:Myc protein, mouse; D050814:Octamer Transcription Factor-3; C456265:Og2x protein, mouse; C494174:Pou5f1 protein, mouse; D011506:Proteins; D016271:Proto-Oncogene Proteins c-myc; D022661:RNA, Untranslated; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; D014157:Transcription Factors