title: Activation of pluripotency genes by a nanotube-mediated protein delivery system.
abstract: The overexpression of cell reprogramming factors (Oct4, Sox2, Klf4, Nanog, and c-Myc) allows differentiated cells to revertto an earlier developmental stage. Differentiated cells can also be reprogrammed by directly delivering reprogramming proteins tagged with cell-penetrating peptides, which allow the proteins to pass through the cell membrane and into the cytoplasm-although this method has been an inefficient process. Here, we describe a novel technique for delivering reprogramming proteins into cells using titanium oxide (TiO2 ) nanotubes, which show no cytotoxic effects and do not affect cell proliferation. TiO2 nanotubes successfully transferred the above-mentioned reprogramming factors into differentiated somatic cells. After 3 weeks of treatment with protein-conjugated nanotubes, the somatic cells adopted an embryonic stem cell-like morphology and expressed activated Oct4-green fluorescent protein, a pluripotency biomarker. Our results indicate that TiO2 nanotubes can be used to directly deliver reprogramming factors into somatic cells to induce pluripotency.
authors.affiliation: Samsung Electronics, Suwon, Gyeonggi-do, Republic of Korea.
authors.forename: Seong Je
authors.initials: SJ
authors.lastname: Cho
authors.forename: Hyun Woo
authors.initials: HW
authors.lastname: Choi
authors.forename: Jaegeol
authors.initials: J
authors.lastname: Cho
authors.forename: Suntae
authors.initials: S
authors.lastname: Jung
authors.forename: Han Geuk
authors.initials: HG
authors.lastname: Seo
authors.forename: Jeong Tae
authors.initials: JT
authors.lastname: Do
mesh_terms: D000818:Animals; D054337:Cell Dedifferentiation / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D002478:Cells, Cultured; D065150:Cellular Reprogramming / Q000235:genetics*; D053595:Embryonic Stem Cells; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D018398:Homeodomain Proteins / Q000096:biosynthesis; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000096:biosynthesis; D053768:Metal Nanoparticles; D051379:Mice; D008822:Mice, Transgenic; D000071317:Nanog Homeobox Protein; D043942:Nanotubes; D050814:Octamer Transcription Factor-3 / Q000096:biosynthesis / Q000235:genetics; D021381:Protein Transport / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D055748:SOXB1 Transcription Factors / Q000096:biosynthesis; D014025:Titanium / Q000494:pharmacology*
chemical_list: D018398:Homeodomain Proteins; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; C489428:Myc protein, mouse; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D016271:Proto-Oncogene Proteins c-myc; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; D049452:Green Fluorescent Proteins; C009495:titanium dioxide; D014025:Titanium