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Divergent reprogramming routes lead to alternative stem-cell states

机译:不同的重编程途径导致替代的干细胞状态

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摘要

Plurpotency is definde by the ability of a cell to differentiate to the derivatives of all the three embryonic germ layers: ectoderm, mesoderm and endoderm. Pluripotent cells can be captured via the archetypal derivation of embryonic stem cells or via somatic cell reprogramming. Somatic cells are induced to acquire a pluripotent stem cell (iPSC) state through the forced expression of key transcription factors, and in the mouse these cells can fulfil the strictest of all developmental assays for pluiipotent cells by generating completely iPSC-derived embryos and mice. However, it is not known whether there are additional classes of pluiipotent cells, or what the spectrum of reprogrammed phenotypes encompasses. Here we explore alternative outcomes of somatic reprogramming by fully characterizing reprogrammed cells independent of preconceived definitions of iPSC states. We demonstrate that by maintaining elevated reprogramming factor expression levels, mouse embryonic fibroblasts go through unique epigenetic modifications to arrive at a stable, Nanog-positive, alternative pluiipotent state. In doing so, we prove that the pluripotent spectrum can encompass multiple, unique cell states.%"Project Grandiose"联合项目组的研究人员,在本期Nature上发表的两篇论文中和在Nature Communications上同时发表的三篇论文中,报告了他们为表征与由转录因子介导的向多能性的重新编程有关的蛋白、DNA和RNA变化所做工作。在第一篇Nature论文中,Andras Nagy及同事报告说,当要让小鼠胚胎成纤维细胞表达高水平的重新编程因子时,它们会达到另一种状态,即多能稳定状态,该状态被称为F-class(这里的“F”是英文'Fuzzy'的第一个字母,原因是细胞群在培养中外观是“模糊”的)。第二篇论文对描述实现多能性的途径的转录组、表观基因组和蛋白质组数据集进行了广泛分析。它们描述了实现诱导多能性的几个路径的存在,这些路径以截然不同的表观遗传事件为特征。在一篇News & Views文章中,Juan Carlos Izpisua Belmonte在其他最新研究工作的背景下对所有五篇论文的结果进行了讨论,并对多能性的另类状态之存在的可能性进行了推测。
机译:多能性由细胞分化为所有三个胚芽层:外胚层,中胚层和内胚层的衍生物的能力决定。可以通过胚胎干细胞的原型衍生或通过体细胞重编程来捕获多能细胞。通过关键转录因子的强制表达诱导体细胞获得多能干细胞(iPSC)状态,并且在小鼠中,这些细胞通过生成完全由iPSC衍生的胚胎和小鼠,可以满足所有多能细胞发展试验中最严格的要求。但是,尚不知道是否还有其他类型的全能细胞,或者涵盖了重编程表型的范围。在这里,我们通过完全表征独立于iPSC状态的预定义定义的重编程细胞,探索体细胞重编程的替代结果。我们证明,通过维持升高的重编程因子表达水平,小鼠胚胎成纤维细胞经过独特的表观遗传修饰,以达到稳定的,Nanog阳性,替代性多能状态。这样,我们证明了多能谱可以包含多个唯一的细胞状态。%“宏伟计划”联合项目组的研究人员,在本期自然上发表的两篇论文中和在自然通讯上同时发表的三篇论文中,报告了他们为表征与由转录因子介导的向多能性的重新编程有关的蛋白。DNA和RNA变化处理工作。在第一篇自然论文中,Andras Nagy及同事报告说,当要让小鼠体内成纤维细胞表达高水平的重新编程因子时,它们会达到另一种状态,即多能稳定状态,该状态被称为F-class(这里的“ F”是英文'Fuzzy第二篇论文对描述实现多能性的途径的转录组,表观基因组和蛋白质组数据集进行了广泛的分析。'的第一个字母,原因是细胞群在培养中外观是“模糊”的)。 。它们描述了实现感应多能性的几个路径的存在,这些路径以截然不同的表观遗传事件为特征。在新闻与评论文章中,Juan Carlos Izpisua Belmonte在其他最新研究工作的背景下对所有五篇论文的结果进行了讨论,替代多能性的另一类状态之存在的可能进行了推测。

著录项

  • 来源
    《Nature》 |2014年第7530期|192-197a2|共7页
  • 作者单位

    Lnenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada;

    Lnenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada,Institute of Medical Science, University of Toronto, Toronto, Ontario M5T 3H7, Canada;

    Lnenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada;

    Lnenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada;

    Lnenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada,Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5T 3H7, Canada;

    Lnenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada,Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5T 3H7, Canada;

    Lnenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada;

    Genomic Medicine Institute, Medical Research Center, Seoul National University, Seoul 110-799, South Korea,Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 110-799, South Korea,Department of Biochemistry, Seoul National University College of Medicine, Seoul 110-799, South Korea;

    Department of Systems & Computational Biology, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York 10461, USA;

    Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072, Australia,QIMR Berghofer Medical Research Institute, Genomic Biology Lab, 300 Herston Road, Brisbane, Queensland 4006, Australia;

    Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072, Australia;

    Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072, Australia;

    Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Queensland 4072, Australia;

    Genome Biology Department, The John Curtin School of Medical Research, The Australian National University, Acton (Canberra), Australian Capital Territory 2601, Australia;

    Genome Biology Department, The John Curtin School of Medical Research, The Australian National University, Acton (Canberra), Australian Capital Territory 2601, Australia,Victor Chang Cardiac Research Institute, Darlinghurst (Sydney), New South Wales 2010, Australia;

    Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072, Australia;

    Genomic Medicine Institute, Medical Research Center, Seoul National University, Seoul 110-799, South Korea,Life Science Institute, Macrogen Inc., Seoul 153-781, South Korea;

    Genomic Medicine Institute, Medical Research Center, Seoul National University, Seoul 110-799, South Korea,Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 110-799, South Korea,Department of Biochemistry, Seoul National University College of Medicine, Seoul 110-799, South Korea,Life Science Institute, Macrogen Inc., Seoul 153-781, South Korea;

    Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Queensland 4072, Australia;

    Lnenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada,Department of Physiology, University of Toronto, Toronto, Ontario M5T 3H7, Canada,Department of Obstetrics and Gynaecology, University of Toronto, Toronto, Ontario M5T 3H7, Canada;

    Lnenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada,Institute of Medical Science, University of Toronto, Toronto, Ontario M5T 3H7, Canada,Department of Obstetrics and Gynaecology, University of Toronto, Toronto, Ontario M5T 3H7, Canada;

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