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Transcriptome transfer produces a predictable cellular phenotype

机译:转录组转移产生可预测的细胞表型

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摘要

Cellular phenotype is the conglomerate of multiple cellular processes involving gene and protein expression that result in the elaboration of a cell's particular morphology and function. It has been thought that differentiated postmitotic cells have their genomes hard wired, with little ability for phenotypic plasticity. Here we show that transfer of the transcriptome from differentiated rat astrocytes into a nondi-viding differentiated rat neuron resulted in the conversion of the neuron into a functional astrocyte-like cell in a time-dependent manner. This single-cell study permits high resolution of molecular and functional components that underlie phenotype identity. The RNA population from astrocytes contains RNAs in the appropriate relative abundances that give rise to regulatory RNAs and translated proteins that enable astrocyte identity. When transferred into the postmitotic neuron, the astrocyte RNA population converts 44% of the neuronal host cells into the destination astrocyte-like phenotype. In support of this observation, quantitative measures of cellular morphology, single-cell PCR, single-cell microarray, and single-cell functional analyses have been performed. The host-cell phenotypic changes develop over many weeks and are persistent. We call this process of RNA-induced phenotype changes, transcriptome-induced phenotype remodeling.
机译:细胞表型是涉及基因和蛋白质表达的多个细胞过程的集合体,这些过程导致细胞特定形态和功能的完善。认为分化的有丝分裂后细胞的基因组是硬连接的,具有很少的表型可塑性。在这里,我们显示转录组从分化的大鼠星形胶质细胞转移到非分裂的分化的大鼠神经元中,导致神经元以时间依赖性方式转化为功能性星形胶质样细胞。这项单细胞研究允许对构成表型同一性的分子和功能成分进行高分辨率分析。来自星形胶质细胞的RNA群体含有适当相对丰度的RNA,这些RNA会产生调节性RNA和翻译的蛋白质,从而使星形胶质细胞具有同一性。当转移到有丝分裂后神经元中时,星形胶质细胞RNA群体将44%的神经元宿主细胞转化为目的星形胶质细胞样表型。为了支持该观察,已经进行了细胞形态学,单细胞PCR,单细胞微阵列和单细胞功能分析的定量测量。宿主细胞的表型变化会持续数周并持续存在。我们称此过程为RNA诱导的表型改变,转录组诱导的表型重塑。

著录项

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  • 作者单位

    Departments of Pharmacology, University of Pennsylvania, Philadelphia, PA 19104;

    Departments of Pharmacology, University of Pennsylvania, Philadelphia, PA 19104;

    Departments of Pharmacology, University of Pennsylvania, Philadelphia, PA 19104 Shanghai Institute of Medical Genetics and Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai 200040, Peoples Republic of China;

    Departments of Pharmacology, University of Pennsylvania, Philadelphia, PA 19104;

    Penn Genome Frontiers Institute, University of Pennsylvania, Philadelphia, PA 19104 Biology, University of Pennsylvania, Philadelphia, PA 19104;

    Departments of Pharmacology, University of Pennsylvania, Philadelphia, PA 19104;

    Departments of Pharmacology, University of Pennsylvania, Philadelphia, PA 19104;

    Departments of Pharmacology, University of Pennsylvania, Philadelphia, PA 19104 Penn Genome Frontiers Institute, University of Pennsylvania, Philadelphia, PA 19104;

    Mechanical Engineering and Applied Mechanics, University of Pennsylvania, Philadelphia, PA 19104;

    Neuroscience, University of Pennsylvania, Philadelphia, PA 19104;

    Department of Physiology, Wonkwang University School of Medicine, Iksan 570-749, South Korea;

    Penn Genome Frontiers Institute, University of Pennsylvania, Philadelphia, PA 19104 Mechanical Engineering and Applied Mechanics, University of Pennsylvania, Philadelphia, PA 19104;

    Penn Genome Frontiers Institute, University of Pennsylvania, Philadelphia, PA 19104 Bioengineering, University of Pennsylvania, Philadelphia, PA 19104;

    Penn Genome Frontiers Institute, University of Pennsylvania, Philadelphia, PA 19104 Biology, University of Pennsylvania, Philadelphia, PA 19104;

    Departments of Pharmacology, University of Pennsylvania, Philadelphia, PA 19104 Penn Genome Frontiers Institute, University of Pennsylvania, Philadelphia, PA 19104 Psychiatry, University of Pennsylvania, Philadelphia, PA 19104;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    neuron; transcriptome-induced phenotype remodeling; single cell; waddington;

    机译:神经元转录组诱导的表型重塑;单细胞沃丁顿;

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