Abstract
Somatic cell nuclear transfer allows trans-acting factors present in the mammalian oocyte to reprogram somatic cell nuclei to an undifferentiated state. We show that four factors (OCT4, SOX2, NANOG, and LIN28) are sufficient to reprogram human somatic cells to pluripotent stem cells that exhibit the essential characteristics of embryonic stem (ES) cells. These induced pluripotent human stem cells have normal karyotypes, express telomerase activity, express cell surface markers and genes that characterize human ES cells, and maintain the developmental potential to differentiate into advanced derivatives of all three primary germ layers. Such induced pluripotent human cell lines should be useful in the production of new disease models and in drug development, as well as for applications in transplantation medicine, once technical limitations (for example, mutation through viral integration) are eliminated.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Differentiation
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Cell Line*
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Cell Proliferation
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Cell Shape
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Cellular Reprogramming*
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / physiology
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Embryonic Stem Cells / cytology
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Fetus
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Fibroblasts / cytology*
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HMGB Proteins / genetics
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HMGB Proteins / physiology
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Homeodomain Proteins / genetics
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Homeodomain Proteins / physiology
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Humans
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Infant, Newborn
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Karyotyping
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Mice
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Mice, SCID
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Nanog Homeobox Protein
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Octamer Transcription Factor-3 / genetics
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Octamer Transcription Factor-3 / physiology
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Oligonucleotide Array Sequence Analysis
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Pluripotent Stem Cells / cytology*
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Pluripotent Stem Cells / physiology
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RNA-Binding Proteins / genetics
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RNA-Binding Proteins / physiology
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SOXB1 Transcription Factors
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Stem Cell Transplantation
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Teratoma / pathology
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Transcription Factors / genetics
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Transcription Factors / physiology
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Transduction, Genetic
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Transgenes
Substances
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DNA-Binding Proteins
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HMGB Proteins
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Homeodomain Proteins
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Lin28A protein, human
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NANOG protein, human
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Nanog Homeobox Protein
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Octamer Transcription Factor-3
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RNA-Binding Proteins
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SOX2 protein, human
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SOXB1 Transcription Factors
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Sox2 protein, mouse
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Transcription Factors