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Journal ArticleDOI

Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors

30 Nov 2007-Cell (Cell)-Vol. 131, Iss: 5, pp 861-872
TL;DR: It is demonstrated that iPS cells can be generated from adult human fibroblasts with the same four factors: Oct3/4, Sox2, Klf4, and c-Myc.
About: This article is published in Cell.The article was published on 2007-11-30 and is currently open access. It has received 18175 citations till now. The article focuses on the topics: Induced pluripotent stem cell & Embryonic stem cell.
Citations
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Journal ArticleDOI
07 Nov 2008-Science
TL;DR: This work generated mouse induced pluripotent stem cells from fibroblasts and liver cells by using nonintegrating adenoviruses transiently expressing Oct4, Sox2, Klf4, and c-Myc, providing strong evidence that insertional mutagenesis is not required for in vitro reprogramming.
Abstract: Pluripotent stem cells have been generated from mouse and human somatic cells by viral expression of the transcription factors Oct4, Sox2, Klf4, and c-Myc. A major limitation of this technology is the use of potentially harmful genome-integrating viruses. We generated mouse induced pluripotent stem (iPS) cells from fibroblasts and liver cells by using nonintegrating adenoviruses transiently expressing Oct4, Sox2, Klf4, and c-Myc. These adenoviral iPS (adeno-iPS) cells show DNA demethylation characteristic of reprogrammed cells, express endogenous pluripotency genes, form teratomas, and contribute to multiple tissues, including the germ line, in chimeric mice. Our results provide strong evidence that insertional mutagenesis is not required for in vitro reprogramming. Adenoviral reprogramming may provide an improved method for generating and studying patient-specific stem cells and for comparing embryonic stem cells and iPS cells.

1,714 citations

Journal ArticleDOI
TL;DR: A simple method is reported, using p53 suppression and nontransforming L-Myc, to generate human induced pluripotent stem cells (iPSCs) with episomal plasmid vectors, which may provide iPSCs suitable for autologous and allologous stem-cell therapy in the future.
Abstract: Human induced pluripotent stem cells are generated with episomal plasmid vectors at increased efficiency using non-transforming L-Myc and knockdown of p53 Also in this issue, Chen et al report defined conditions for human cell reprogramming and culture

1,712 citations

Journal ArticleDOI
22 Feb 2008-Cell
TL;DR: The potential to generate virtually any differentiated cell type from embryonic stem cells (ESCs) offers the possibility to establish new models of mammalian development and to create new sources of cells for regenerative medicine, but it is essential to be able to control ESC differentiation and to direct the development of these cells along specific pathways.

1,695 citations


Cites background from "Induction of Pluripotent Stem Cells..."

  • ...Importantly, Takahashi et al. (2007) showed that the human iPS cells could be directed down the cardiomyocyte lineage using activin/ BMP4 and toward neurons using PA6 stromal cell coculture....

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  • ...Additionally, the ability to derive patient-specific ESC equivalents (Park et al., 2008; Takahashi et al., 2007; Yu et al., 2007) provides powerful new tools to evade the immune system, study basic disease mechanisms, and establish screens for drug discovery (see Review by R. Jaenisch and R. Young,…...

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  • ...These studies demonstrated reprogramming of either the differentiated progeny of stem cells (Park et al., 2008), fetal and neonatal fibroblasts (Yu et al., 2007), or adult fibroblasts (Takahashi et al., 2007)....

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Journal ArticleDOI
TL;DR: Valproic acid (VPA), an HDAC inhibitor, improves reprogramming efficiency by more than 100-fold, using Oct4-GFP as a reporter and enables efficient induction of pluripotent stem cells without introduction of the oncogene c-Myc.
Abstract: Existing methods for reprogramming somatic cells to 'induced pluripotent stem cells' are inefficient, with only a small fraction of the starting cell population becoming pluripotent. Working with mouse embryonic fibroblasts, Hunagfu et al. increase reprogramming efficiency by treatment with DNA methyltransferase and histone deacetylase inhibitors. Reprogramming of mouse and human somatic cells can be achieved by ectopic expression of transcription factors, but with low efficiencies. We report that DNA methyltransferase and histone deacetylase (HDAC) inhibitors improve reprogramming efficiency. In particular, valproic acid (VPA), an HDAC inhibitor, improves reprogramming efficiency by more than 100-fold, using Oct4-GFP as a reporter. VPA also enables efficient induction of pluripotent stem cells without introduction of the oncogene c-Myc.

1,691 citations

Journal ArticleDOI
TL;DR: This article will review the isolation and characterization of the properties of different dental MSC-like populations in comparison with those of other MSCs, such as BMMSCs.
Abstract: To date, 5 different human dental stem/progenitor cells have been isolated and characterized: dental pulp stem cells (DPSCs), stem cells from exfoliated deciduous teeth (SHED), periodontal ligament stem cells (PDLSCs), stem cells from apical papilla (SCAP), and dental follicle progenitor cells (DFPCs). These post-natal populations have mesenchymal-stem-cell-like (MSC) qualities, including the capacity for self-renewal and multilineage differentiation potential. MSCs derived from bone marrow (BMMSCs) are capable of giving rise to various lineages of cells, such as osteogenic, chondrogenic, adipogenic, myogenic, and neurogenic cells. The dental-tissue-derived stem cells are isolated from specialized tissue with potent capacities to differentiate into odontogenic cells. However, they also have the ability to give rise to other cell lineages similar to, but different in potency from, that of BMMSCs. This article will review the isolation and characterization of the properties of different dental MSC-like populations in comparison with those of other MSCs, such as BMMSCs. Important issues in stem cell biology, such as stem cell niche, homing, and immunoregulation, will also be discussed.

1,643 citations

References
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Journal ArticleDOI
25 Aug 2006-Cell
TL;DR: Induction of pluripotent stem cells from mouse embryonic or adult fibroblasts by introducing four factors, Oct3/4, Sox2, c-Myc, and Klf4, under ES cell culture conditions is demonstrated and iPS cells, designated iPS, exhibit the morphology and growth properties of ES cells and express ES cell marker genes.

23,959 citations


"Induction of Pluripotent Stem Cells..." refers background in this paper

  • ...We showed that induced pluripotent stem (iPS) cells can be generated from mouse embryonic fibroblasts (MEF) and adult mouse tail-tip fibroblasts by the retrovirus-mediated transfection of four transcription factors, namely Oct3/4, Sox2, c-Myc, and Klf4 (Takahashi and Yamanaka, 2006)....

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  • ...Induction of iPS cells from mouse fibroblasts requires retroviruses with high transduction efficiencies (Takahashi and Yamanaka, 2006)....

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  • ...Optimization of Retroviral Transduction for Generating Human iPS Cells Induction of iPS cells from mouse fibroblasts requires retroviruses with high transduction efficiencies (Takahashi and Yamanaka, 2006)....

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Journal ArticleDOI
06 Nov 1998-Science
TL;DR: Human blastocyst-derived, pluripotent cell lines are described that have normal karyotypes, express high levels of telomerase activity, and express cell surface markers that characterize primate embryonic stem cells but do not characterize other early lineages.
Abstract: Human blastocyst-derived, pluripotent cell lines are described that have normal karyotypes, express high levels of telomerase activity, and express cell surface markers that characterize primate embryonic stem cells but do not characterize other early lineages. After undifferentiated proliferation in vitro for 4 to 5 months, these cells still maintained the developmental potential to form trophoblast and derivatives of all three embryonic germ layers, including gut epithelium (endoderm); cartilage, bone, smooth muscle, and striated muscle (mesoderm); and neural epithelium, embryonic ganglia, and stratified squamous epithelium (ectoderm). These cell lines should be useful in human developmental biology, drug discovery, and transplantation medicine.

15,555 citations


"Induction of Pluripotent Stem Cells..." refers background in this paper

  • ...These properties have led to expectations that human ES cells might be useful to understand disease mechanisms, to screen effective and safe drugs, and to treat patients of various diseases and injuries, such as juvenile diabetes and spinal cord injury (Thomson et al., 1998)....

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Journal ArticleDOI
09 Jul 1981-Nature
TL;DR: The establishment in tissue culture of pluripotent cell lines which have been isolated directly from in vitro cultures of mouse blastocysts are reported, able to differentiate either in vitro or after innoculation into a mouse as a tumour in vivo.
Abstract: Pluripotential cells are present in a mouse embryo until at least an early post-implantation stage, as shown by their ability to take part hi the formation of chimaeric animals1 and to form teratocarcinomas2. Until now it has not been possible to establish progressively growing cultures of these cells in vitro, and cell lines have only been obtained after teratocarcinoma formation in vivo. We report here the establishment in tissue culture of pluripotent cell lines which have been isolated directly from in vitro cultures of mouse blastocysts. These cells are able to differentiate either in vitro or after innoculation into a mouse as a tumour in vivo. They have a normal karyotype.

8,144 citations


"Induction of Pluripotent Stem Cells..." refers background in this paper

  • ...Embryonic stem (ES) cells, derived from the inner cell mass of mammalian blastocysts, have the ability to grow indefinitely while maintaining pluripotency (Evans and Kaufman, 1981; Martin, 1981)....

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Journal ArticleDOI
TL;DR: In this article, the authors described the establishment directly from normal preimplantation mouse embryos of a cell line that forms teratocarcinomas when injected into mice and demonstrated the pluripotency of these embryonic stem cells by the observation that subclonal cultures, derived from isolated single cells, can differentiate into a wide variety of cell types.
Abstract: This report describes the establishment directly from normal preimplantation mouse embryos of a cell line that forms teratocarcinomas when injected into mice. The pluripotency of these embryonic stem cells was demonstrated conclusively by the observation that subclonal cultures, derived from isolated single cells, can differentiate into a wide variety of cell types. Such embryonic stem cells were isolated from inner cell masses of late blastocysts cultured in medium conditioned by an established teratocarcinoma stem cell line. This suggests that such conditioned medium might contain a growth factor that stimulates the proliferation or inhibits the differentiation of normal pluripotent embryonic cells, or both. This method of obtaining embryonic stem cells makes feasible the isolation of pluripotent cells lines from various types of noninbred embryo, including those carrying mutant genes. The availability of such cell lines should made possible new approaches to the study of early mammalian development.

5,496 citations

Journal ArticleDOI
23 Sep 2005-Cell
TL;DR: Insight is provided into the transcriptional regulation of stem cells and how OCT4, SOX2, and NANOG contribute to pluripotency and self-renewal and how they collaborate to form regulatory circuitry consisting of autoregulatory and feedforward loops.

4,447 citations


"Induction of Pluripotent Stem Cells..." refers background in this paper

  • ...The function of Oct3/4 and Sox2 as core transcription factors to determine pluripotency is well documented (Boyer et al., 2005; Loh et al., 2006; Wang et al., 2006)....

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