Late passage human fibroblasts induced to pluripotency are capable of directed neuronal differentiation.
It is possible to generate induced pluripotent stem (iPS) cells from mouse and human somatic cells by ectopic expression of defined sets of transcription factors. However, the recommendation that somatic cells should be utilized at early passages for induced reprogramming limits their therapeutic application. Here we report successful reprogramming of human fibroblasts after more than 20 passages in vitro, to a pluripotent state with four transcription factors: Oct4, Sox2, Klf4, and c-Myc. The late passage-derived human iPS cells resemble human embryonic stem cells in morphology, cell surface antigens, pluripotent gene expression profiles, and epigenetic states. Moreover, these iPS cells differentiate into cell types representative of the three germ layers in teratomas in vivo, and directed neuronal differentiation in vitro.
Liu
Jun
J
Centre for Reproduction and Development, Monash Institute of Medical Research, Monash University, Clayton, Victoria, Australia.
Sumer
Huseyin
H
Leung
Jessie
J
Upton
Kyle
K
Dottori
Mirella
M
Pébay
Alice
A
Verma
Paul J
PJ
D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D005347:Fibroblasts / Q000166:cytology*; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D007621:Karyotyping; D000090062:Kruppel-Like Factor 4; D051379:Mice; D016513:Mice, SCID; D000071317:Nanog Homeobox Protein; D009432:Neural Crest / Q000166:cytology; D009474:Neurons / Q000166:cytology*; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA; D013194:Staining and Labeling; D013724:Teratoma / Q000473:pathology
D018398:Homeodomain Proteins; C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3