De-differentiation of mouse interfollicular keratinocytes by the embryonic transcription factor Oct-4.
The embryonic transcription factor Oct-4 is often referred to as the master regulator of the undifferentiated state. Although its role in maintaining embryonic stem (ES) cell pluripotency is well established, its ability to directly reprogram committed somatic cells is not well defined. Using transient transfection, we tested its ability to revert mouse interfollicular epidermal basal keratinocytes to a more ES cell-like state. We found that the Oct-4-transfected keratinocytes expressed the Oct-4 target genes, Sox-2, Nanog, undifferentiated transcription factor 1 (Utf1), and Rex-1. We also noted an increase in developmental potential caused by Oct-4, with the transfected cells able to differentiate into neuronal cells when exposed to neuroectodermal differentiation medium. Control-transfected keratinocytes were unable to respond to the medium, and remained as keratinocytes. These findings suggest that Oct-4 may be the master regulator of the pluripotent state and demonstrate that differentiated somatic cells can be reverted into more developmentally potent cells through the use of a single factor. The latter finding has great implications for therapeutic cell-replacement applications using cells from easily accessible adult tissues, such as the skin.
Grinnell
Katie L
KL
Department of Anatomy and Cell Biology, The University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA.
Yang
Baoli
B
Eckert
Richard L
RL
Bickenbach
Jackie R
JR
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D003470:Culture Media / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism; D015536:Down-Regulation; D004475:Ectoderm / Q000502:physiology; D053595:Embryonic Stem Cells / Q000166:cytology / Q000502:physiology; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression; D005786:Gene Expression Regulation; D006609:High Mobility Group Proteins / Q000378:metabolism; D007381:Intermediate Filament Proteins / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism*; D017933:Peripheral Nervous System / Q000196:embryology; D010641:Phenotype; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000502:physiology; D055748:SOXB1 Transcription Factors; D014018:Tissue Distribution; D014162:Transfection
D015415:Biomarkers; D003470:Culture Media; D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; C492380:NeuN protein, mouse; D009687:Nuclear Proteins; D050814:Octamer Transcription Factor-3; D055748:SOXB1 Transcription Factors; C098693:Sox1 protein, mouse