Park IH, Zhao R, West JA, Yabuuchi A, Huo H, Ince TA, Lerou PH, Lensch MW, Daley GQReprogramming of human somatic cells to pluripotency with defined factors. Nature 451:141-146

Division of Pediatric Hematology/Oncology, Children's Hospital Boston and Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Nature (Impact Factor: 41.46). 02/2008; 451(7175):141-6. DOI: 10.1038/nature06534
Source: PubMed


Pluripotency pertains to the cells of early embryos that can generate all of the tissues in the organism. Embryonic stem cells are embryo-derived cell lines that retain pluripotency and represent invaluable tools for research into the mechanisms of tissue formation. Recently, murine fibroblasts have been reprogrammed directly to pluripotency by ectopic expression of four transcription factors (Oct4, Sox2, Klf4 and Myc) to yield induced pluripotent stem (iPS) cells. Using these same factors, we have derived iPS cells from fetal, neonatal and adult human primary cells, including dermal fibroblasts isolated from a skin biopsy of a healthy research subject. Human iPS cells resemble embryonic stem cells in morphology and gene expression and in the capacity to form teratomas in immune-deficient mice. These data demonstrate that defined factors can reprogramme human cells to pluripotency, and establish a method whereby patient-specific cells might be established in culture.

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    • "Induced pluripotent stem cells (iPSCs) have similar properties as embryonic stem cells (ESCs), such as self-renewal and differentiation capacity (Park et al., 2008c; Takahashi and Yamanaka, 2006). Reprogramming technique offers tremendous potential for disease modeling, cell-based therapy , and drug screening (Park et al., 2008a). "
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    ABSTRACT: Reprogramming of somatic cells produces induced pluripotent stem cells (iPSCs) that are invaluable resources for biomedical research. Here, we extended the previous transcriptome studies by performing RNA-seq on cells defined by a combination of multiple cellular surface markers. We found that transcriptome changes during early reprogramming occur independently from the opening of closed chromatin by OCT4, SOX2, KLF4, and MYC (OSKM). Furthermore, our data identify multiple spliced forms of genes uniquely expressed at each progressive stage of reprogramming. In particular, we found a pluripotency-specific spliced form of CCNE1 that is specific to human and significantly enhances reprogramming. In addition, single nucleotide polymorphism (SNP) expression analysis reveals that monoallelic gene expression is induced in the intermediate stages of reprogramming, while biallelic expression is recovered upon completion of reprogramming. Our transcriptome data provide unique opportunities in understanding human iPSC reprogramming. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
    Full-text · Article · May 2015 · Stem Cell Reports
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    • "Recently, however, a novel potential source for cardiac cell regeneration has been suggested and that is cardiomyocytes derived from human induced pluripotent stem cells (hiPSCs). Dedifferentiation from adult human dermal fibroblasts goes sequentialy, through transduction of a defined set of transcription factors to dermal fibroblasts to reprogram them back to an equivalent of the early embryonic state (Takahashi et al. 2007 ; Yamanaka 2007 ; Yu et al. 2007 ; Park et al. 2008). It has been reported as hiPSCs resemble human embryonic stem cells (hESCs) in terms of the remarkable self-renewal capacity and undisputed potential for differentiation into three germ layers, including mesoderm, that will give rise to genuine cardiomyocytes (Zhang et al. 2009 ; Zwi et al. 2009). "
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    • "Induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs) share some similarities to cancer cells, including the capacity to bypass senescence and form tumors upon transplantation (Goding et al., 2014). Accordingly, some genes often associated with cancer, such as Myc (Nakagawa et al., 2008; Wernig et al., 2008), p53 (Krizhanovsky and Lowe, 2009), and telomerase (Batista et al., 2011; Park et al., 2008), have been implicated in cellular reprogramming. Additionally, two reprogramming factors, Oct4 and Sox2, can be oncogenic in some cellular contexts (Hochedlinger et al., 2005; Lu et al., 2010; Rudin et al., 2012; Sarkar and Hochedlinger, 2013). "
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    ABSTRACT: Mutations in the retinoblastoma tumor suppressor gene Rb are involved in many forms of human cancer. In this study, we investigated the early consequences of inactivating Rb in the context of cellular reprogramming. We found that Rb inactivation promotes the reprogramming of differentiated cells to a pluripotent state. Unexpectedly, this effect is cell cycle independent, and instead reflects direct binding of Rb to pluripotency genes, including Sox2 and Oct4, which leads to a repressed chromatin state. More broadly, this regulation of pluripotency networks and Sox2 in particular is critical for the initiation of tumors upon loss of Rb in mice. These studies therefore identify Rb as a global transcriptional repressor of pluripotency networks, providing a molecular basis for previous reports about its involvement in cell fate pliability, and implicate misregulation of pluripotency factors such as Sox2 in tumorigenesis related to loss of Rb function.
    Full-text · Article · Jan 2015 · Cell Stem Cell
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