title: Partial somatic to stem cell transformations induced by cell-permeable reprogramming factors.
abstract: The production of pluripotent stem cells (iPSCs) for therapeutic applications will require practical methods to achieve tight temporal and quantitative control of reprogramming factor (RF) expression, while avoiding the mutagenic potential of gene transfer. Toward this end, we have developed cell-permeable RF proteins (CP-RFs) incorporating newly developed macromolecule transduction domains (MTDs). Treatment of human dermal fibroblasts (HDFs) with combinations of cell-permeable OCT4, SOX2, KLF4, CMYC and either NANOG or LIN28 proteins induced the outgrowth of stem cell-like colonies (iSCs). iSC colonies generated with CP-RFs resembled embryonic stem cells with regard to morphology, biomarker expression, and extended capacity for self-renewal, but failed to expand as iPSC or ES cell lines. Partial reprogramming appears to be a common response to protein-based delivery of programming factors into somatic cells.
authors.affiliation: 1] ProCell R&D Institute, ProCell Therapeutics, Inc., Ace-Twin Tower II, Guro3-dong, Guro-gu, Seoul 152-790, Korea [2].
authors.forename: Junghee
authors.initials: J
authors.lastname: Lim
authors.affiliation: 1] ProCell R&D Institute, ProCell Therapeutics, Inc., Ace-Twin Tower II, Guro3-dong, Guro-gu, Seoul 152-790, Korea [2].
authors.forename: Junghee
authors.initials: J
authors.lastname: Kim
authors.affiliation: ProCell R&D Institute, ProCell Therapeutics, Inc., Ace-Twin Tower II, Guro3-dong, Guro-gu, Seoul 152-790, Korea.
authors.forename: Jinsun
authors.initials: J
authors.lastname: Kang
authors.affiliation: 1] ProCell R&D Institute, ProCell Therapeutics, Inc., Ace-Twin Tower II, Guro3-dong, Guro-gu, Seoul 152-790, Korea [2] Department of Biomedical Sciences, Chonnam National University Medical School, 5 Hak-dong, Dong-gu, Kwangju 501-757, Korea [3] Departments of Surgery, Vanderbilt University School of Medicine, 2215B Garland Avenue, Nashville, TN 37232, USA.
authors.forename: Daewoong
authors.initials: D
authors.lastname: Jo
mesh_terms: D002454:Cell Differentiation; D002463:Cell Membrane Permeability; D057846:Cell-Penetrating Peptides / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D065150:Cellular Reprogramming; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D015870:Gene Expression; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism*; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: D057846:Cell-Penetrating Peptides; D018398:Homeodomain Proteins; C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; C000715187:Lin28A protein, human; C489427:MYC protein, human; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D016271:Proto-Oncogene Proteins c-myc; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors