Article

Induction Of Pluripotent Stem Cells From Adult Human Fibroblasts By Defined Factors

Department of Stem Cell Biology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.
Cell (Impact Factor: 33.12). 12/2007; 131(5):861-72. DOI: 10.1016/j.cell.2007.11.019
Source: PubMed

ABSTRACT Successful reprogramming of differentiated human somatic cells into a pluripotent state would allow creation of patient- and disease-specific stem cells. We previously reported generation of induced pluripotent stem (iPS) cells, capable of germline transmission, from mouse somatic cells by transduction of four defined transcription factors. Here, we demonstrate the generation of iPS cells from adult human dermal fibroblasts with the same four factors: Oct3/4, Sox2, Klf4, and c-Myc. Human iPS cells were similar to human embryonic stem (ES) cells in morphology, proliferation, surface antigens, gene expression, epigenetic status of pluripotent cell-specific genes, and telomerase activity. Furthermore, these cells could differentiate into cell types of the three germ layers in vitro and in teratomas. These findings demonstrate that iPS cells can be generated from adult human fibroblasts.

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Available from: Kiichiro Tomoda, Jul 28, 2014
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    • "Recent advancement in stem cell research makes it possible to generate and propagate induced pluripotent stem cells (iPSCs) from skin biopsy or urine samples (containing exfoliated renal epithelial cells; Takahashi et al., 2007; Yu et al., 2007; Zhou et al., 2012). DNA can then be extracted from iPSC cultures for use in genetic analyses. "
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    ABSTRACT: Quality sleep is critical for daily functions of human beings and thus the timing and duration of sleep are tightly controlled. However, rare genetic variants affecting sleep regulatory mechanisms can result in sleep phenotypes of extremely deviated sleep/wake onset time or duration. Using genetic analyses in families with multiple members expressing particular sleep phenotypes, these sleep-associated genetic variants can be identified. Deciphering the nature of these genetic variants using animal models or biochemical methods helps further our understanding of sleep processes. In this chapter, we describe the methods for studying genetics of human sleep behavioral phenotypes. © 2015 Elsevier Inc. All rights reserved.
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    • "To further substantiate our findings, we explored whether reprogramming somatic cells to induced pluripotent stem cells (iPSCs) would recapitulate aberrant methylation patterns specific to undifferentiated cells. Primary fibroblasts with a CTG expansion of approximately 2,000 repeats, which were only partly methylated upstream of the repeats, were reprogrammed according to Takahashi et al. (2007). This resulted in the establishment of three "
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    • "human embryonic stem cells (hESCs) (Thomson et al., 1998) and human induced pluripotent stem cells (hiPSCs) (Takahashi et al., 2007). Accordingly, recent studies have demonstrated the reconstitution in vitro of the specification and development of the mouse germline by PSCs (Hayashi et al., 2011, 2012a): mouse (m) ESCs/iPSCs with ground state pluripotency (Ying et al., 2008) are induced into pre-gastrulation epiblast-like cells (EpiLCs), which are in turn induced into PGC-like cells (PGCLCs) with robust capacity for both spermatogenesis and oogenesis, and for the generation of offspring; these findings suggest a conceptual framework and feasibility for the reconstitution of human germ cell development in vitro. "
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    ABSTRACT: Mechanisms underlying human germ cell development are unclear, partly due to difficulties in studying human embryos and lack of suitable experimental systems. Here, we show that human induced pluripotent stem cells (hiPSCs) differentiate into incipient mesoderm-like cells (iMeLCs), which robustly generate human primordial germ cell-like cells (hPGCLCs) that can be purified using the surface markers EpCAM and INTEGRINα6. The transcriptomes of hPGCLCs and primordial germ cells (PGCs) isolated from non-human primates are similar, and although specification of hPGCLCs and mouse PGCs rely on similar signaling pathways, hPGCLC specification transcriptionally activates germline fate without transiently inducing eminent somatic programs. This includes genes important for naive pluripotency and repression of key epigenetic modifiers, concomitant with epigenetic reprogramming. Accordingly, BLIMP1, which represses somatic programs in mice, activates and stabilizes a germline transcriptional circuit and represses a default neuronal differentiation program. Together, these findings provide a foundation for understanding and reconstituting human germ cell development in vitro. Copyright © 2015 Elsevier Inc. All rights reserved.
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