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  • 1
    Publication Date: 2009-08-12
    Description: Induced pluripotent stem (iPS) cells can be generated from somatic cells by the introduction of Oct3/4 (also known as Pou5f1), Sox2, Klf4 and c-Myc, in mouse and in human. The efficiency of this process, however, is low. Pluripotency can be induced without c-Myc, but with even lower efficiency. A p53 (also known as TP53 in humans and Trp53 in mice) short-interfering RNA (siRNA) was recently shown to promote human iPS cell generation, but the specificity and mechanisms remain to be determined. Here we report that up to 10% of transduced mouse embryonic fibroblasts lacking p53 became iPS cells, even without the Myc retrovirus. The p53 deletion also promoted the induction of integration-free mouse iPS cells with plasmid transfection. Furthermore, in the p53-null background, iPS cells were generated from terminally differentiated T lymphocytes. The suppression of p53 also increased the efficiency of human iPS cell generation. DNA microarray analyses identified 34 p53-regulated genes that are common in mouse and human fibroblasts. Functional analyses of these genes demonstrate that the p53-p21 pathway serves as a barrier not only in tumorigenicity, but also in iPS cell generation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2917235/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2917235/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hong, Hyenjong -- Takahashi, Kazutoshi -- Ichisaka, Tomoko -- Aoi, Takashi -- Kanagawa, Osami -- Nakagawa, Masato -- Okita, Keisuke -- Yamanaka, Shinya -- U01 HL100406/HL/NHLBI NIH HHS/ -- U01 HL100406-01/HL/NHLBI NIH HHS/ -- England -- Nature. 2009 Aug 27;460(7259):1132-5. doi: 10.1038/nature08235. Epub 2009 Aug 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for iPS Cell Research and Application (CiRA), Institute for Integrated Cell-Material Sciences, Kyoto University, Kyoto 606-8507, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19668191" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Animals ; Cell Differentiation ; Cyclin-Dependent Kinase Inhibitor p21/genetics/metabolism ; Embryo, Mammalian/cytology ; Female ; Fibroblasts/cytology/metabolism ; Gene Expression Profiling ; Gene Silencing ; Genes, myc ; Humans ; Male ; Mice ; Oligonucleotide Array Sequence Analysis ; Plasmids/genetics ; Pluripotent Stem Cells/*cytology/*metabolism ; T-Lymphocytes/cytology ; Transfection ; Tumor Suppressor Protein p53/deficiency/genetics/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2007-10-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fukuhara, Atsunori -- Matsuda, Morihiro -- Nishizawa, Masako -- Segawa, Katsumori -- Tanaka, Masaki -- Kishimoto, Kae -- Matsuki, Yasushi -- Murakami, Mirei -- Ichisaka, Tomoko -- Murakami, Hiroko -- Watanabe, Eijiro -- Takagi, Toshiyuki -- Akiyoshi, Megumi -- Ohtsubo, Tsuguteru -- Kihara, Shinji -- Yamashita, Shizuya -- Makishima, Makoto -- Funahashi, Tohru -- Yamanaka, Shinya -- Hiramatsu, Ryuji -- Matsuzawa, Yuji -- Shimomura, Iichiro -- New York, N.Y. -- Science. 2007 Oct 26;318(5850):565.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17962537" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2008-02-16
    Description: Induced pluripotent stem (iPS) cells have been generated from mouse and human fibroblasts by the retroviral transduction of four transcription factors. However, the cell origins and molecular mechanisms of iPS cell induction remain elusive. This report describes the generation of iPS cells from adult mouse hepatocytes and gastric epithelial cells. These iPS cell clones appear to be equivalent to embryonic stem cells in gene expression and are competent to generate germline chimeras. Genetic lineage tracings show that liver-derived iPS cells are derived from albumin-expressing cells. No common retroviral integration sites are found among multiple clones. These data suggest that iPS cells are generated by direct reprogramming of lineage-committed somatic cells and that retroviral integration into specific sites is not required.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Aoi, Takashi -- Yae, Kojiro -- Nakagawa, Masato -- Ichisaka, Tomoko -- Okita, Keisuke -- Takahashi, Kazutoshi -- Chiba, Tsutomu -- Yamanaka, Shinya -- New York, N.Y. -- Science. 2008 Aug 1;321(5889):699-702. doi: 10.1126/science.1154884. Epub 2008 Feb 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Stem Cell Biology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18276851" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blastocyst/cytology ; Cell Differentiation ; Cell Proliferation ; *Cellular Reprogramming ; Chimera ; Clone Cells ; Culture Media ; Embryonic Stem Cells/cytology/metabolism ; Epithelial Cells/*cytology ; Gastric Mucosa/*cytology ; Genetic Vectors ; Hepatocytes/*cytology ; Mice ; Mice, Nude ; Neoplasms/etiology ; Pluripotent Stem Cells/*cytology/metabolism ; Retroviridae/genetics ; Stem Cell Transplantation ; Transcription Factors/genetics ; Transfection ; Virus Integration
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2004-12-18
    Description: Fat tissue produces a variety of secreted proteins (adipocytokines) with important roles in metabolism. We isolated a newly identified adipocytokine, visfatin, that is highly enriched in the visceral fat of both humans and mice and whose expression level in plasma increases during the development of obesity. Visfatin corresponds to a protein identified previously as pre-B cell colony-enhancing factor (PBEF), a 52-kilodalton cytokine expressed in lymphocytes. Visfatin exerted insulin-mimetic effects in cultured cells and lowered plasma glucose levels in mice. Mice heterozygous for a targeted mutation in the visfatin gene had modestly higher levels of plasma glucose relative to wild-type littermates. Surprisingly, visfatin binds to and activates the insulin receptor. Further study of visfatin's physiological role may lead to new insights into glucose homeostasis and/or new therapies for metabolic disorders such as diabetes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fukuhara, Atsunori -- Matsuda, Morihiro -- Nishizawa, Masako -- Segawa, Katsumori -- Tanaka, Masaki -- Kishimoto, Kae -- Matsuki, Yasushi -- Murakami, Mirei -- Ichisaka, Tomoko -- Murakami, Hiroko -- Watanabe, Eijiro -- Takagi, Toshiyuki -- Akiyoshi, Megumi -- Ohtsubo, Tsuguteru -- Kihara, Shinji -- Yamashita, Shizuya -- Makishima, Makoto -- Funahashi, Tohru -- Yamanaka, Shinya -- Hiramatsu, Ryuji -- Matsuzawa, Yuji -- Shimomura, Iichiro -- New York, N.Y. -- Science. 2005 Jan 21;307(5708):426-30. Epub 2004 Dec 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine and Pathophysiology, Graduate School of Medicine, and Department of Organismal Biosystems, Graduate School of Frontier Biosciences, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15604363" target="_blank"〉PubMed〈/a〉
    Keywords: Adipocytes/drug effects/metabolism ; Adipose Tissue/*metabolism ; Animals ; Binding Sites ; Blood Glucose/analysis ; Cell Line ; Cells, Cultured ; Cytokines/blood/genetics/*metabolism/pharmacology ; Diabetes Mellitus, Type 2/metabolism ; Dose-Response Relationship, Drug ; Female ; Gene Expression Profiling ; Gene Expression Regulation/drug effects ; Gene Targeting ; Humans ; Insulin/blood/*metabolism ; Insulin Resistance ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Obese ; Molecular Mimicry ; Muscle Cells/metabolism ; Nicotinamide Phosphoribosyltransferase ; Phosphorylation ; Receptor, Insulin/metabolism ; Recombinant Proteins/pharmacology ; Signal Transduction ; Subcutaneous Tissue ; Viscera
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2011-06-10
    Description: Induced pluripotent stem cells (iPSCs) are generated from somatic cells by the transgenic expression of three transcription factors collectively called OSK: Oct3/4 (also called Pou5f1), Sox2 and Klf4. However, the conversion to iPSCs is inefficient. The proto-oncogene Myc enhances the efficiency of iPSC generation by OSK but it also increases the tumorigenicity of the resulting iPSCs. Here we show that the Gli-like transcription factor Glis1 (Glis family zinc finger 1) markedly enhances the generation of iPSCs from both mouse and human fibroblasts when it is expressed together with OSK. Mouse iPSCs generated using this combination of transcription factors can form germline-competent chimaeras. Glis1 is enriched in unfertilized oocytes and in embryos at the one-cell stage. DNA microarray analyses show that Glis1 promotes multiple pro-reprogramming pathways, including Myc, Nanog, Lin28, Wnt, Essrb and the mesenchymal-epithelial transition. These results therefore show that Glis1 effectively promotes the direct reprogramming of somatic cells during iPSC generation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Maekawa, Momoko -- Yamaguchi, Kei -- Nakamura, Tomonori -- Shibukawa, Ran -- Kodanaka, Ikumi -- Ichisaka, Tomoko -- Kawamura, Yoshifumi -- Mochizuki, Hiromi -- Goshima, Naoki -- Yamanaka, Shinya -- England -- Nature. 2011 Jun 8;474(7350):225-9. doi: 10.1038/nature10106.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for iPS Cell Research and Application, Kyoto University, Kyoto 606-8507, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21654807" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Cells, Cultured ; *Cellular Reprogramming ; DNA-Binding Proteins/*metabolism ; Embryonic Stem Cells/cytology/metabolism ; Epithelial-Mesenchymal Transition ; Female ; Fibroblasts/*cytology/*metabolism ; Gene Expression Profiling ; Genes, myc/genetics ; Hepatocyte Nuclear Factor 3-beta/metabolism ; Homeodomain Proteins/metabolism ; Humans ; Induced Pluripotent Stem Cells/*cytology/*metabolism ; Mice ; Nuclear Transfer Techniques ; Oligonucleotide Array Sequence Analysis ; Protein Binding ; RNA-Binding Proteins/metabolism ; Receptors, Estrogen/metabolism ; Transcription Factors/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 6
    Publication Date: 2008-10-11
    Description: Induced pluripotent stem (iPS) cells have been generated from mouse and human somatic cells by introducing Oct3/4 and Sox2 with either Klf4 and c-Myc or Nanog and Lin28 using retroviruses or lentiviruses. Patient-specific iPS cells could be useful in drug discovery and regenerative medicine. However, viral integration into the host genome increases the risk of tumorigenicity. Here, we report the generation of mouse iPS cells without viral vectors. Repeated transfection of two expression plasmids, one containing the complementary DNAs (cDNAs) of Oct3/4, Sox2, and Klf4 and the other containing the c-Myc cDNA, into mouse embryonic fibroblasts resulted in iPS cells without evidence of plasmid integration, which produced teratomas when transplanted into mice and contributed to adult chimeras. The production of virus-free iPS cells, albeit from embryonic fibroblasts, addresses a critical safety concern for potential use of iPS cells in regenerative medicine.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Okita, Keisuke -- Nakagawa, Masato -- Hyenjong, Hong -- Ichisaka, Tomoko -- Yamanaka, Shinya -- New York, N.Y. -- Science. 2008 Nov 7;322(5903):949-53. doi: 10.1126/science.1164270. Epub 2008 Oct 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for iPS Cell Research and Application (CiRA), Institute for Integrated Cell-Material Sciences, Kyoto University, Kyoto 606-8507, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18845712" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cellular Reprogramming ; Chimera ; DNA, Complementary ; Embryo, Mammalian/cytology ; Embryonic Stem Cells/cytology/metabolism ; Fibroblasts/*cytology/metabolism ; Genes, myc ; Genetic Vectors ; Kruppel-Like Transcription Factors/genetics/metabolism ; Mice ; Octamer Transcription Factor-3/genetics/metabolism ; *Plasmids ; *Pluripotent Stem Cells/cytology/metabolism/transplantation ; Retroviridae/genetics ; SOXB1 Transcription Factors/genetics/metabolism ; Teratoma/etiology ; *Transfection
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
  • 8
    Publication Date: 2010-07-26
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 9
  • 10
    Publication Date: 2013-10-09
    Description: Piwi-interacting RNAs (piRNAs) are gonad-specific small RNAs that provide defense against transposable genetic elements called transposons. Our knowledge of piRNA biogenesis is sketchy, partly due to an incomplete inventory of the factors involved. Here, we identify Tudor domain-containing 12 (TDRD12; also known as ECAT8) as a unique piRNA biogenesis factor...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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