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Diverse reprogramming codes for neuronal identity

机译：神经元身份的多种重编程代码

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摘要

The transcriptional programs that establish neuronal identity evolved to produce the rich diversity of neuronal cell types that arise sequentially during development. Remarkably, transient expression of certain transcription factors can also endow non-neural cells with neuronal properties. The relationship between reprogramming factors and the transcriptional networks that produce neuronal identity and diversity remains largely unknown. Here, from a screen of 598 pairs of transcription factors, we identify 76 pairs of transcription factors that induce mouse fibroblasts to differentiate into cells with neuronal features. By comparing the transcriptomes of these induced neuronal cells (iN cells) with those of endogenous neurons, we define a core cell-autonomous neuronal signature. The iN cells also exhibit diversity; each transcription factor pair produces iN cells with unique transcriptional patterns that can predict their pharmacological responses. By linking distinct transcription factor input codes to defined transcriptional outputs, this study delineates cell-autonomous features of neuronal identity and diversity and expands the reprogramming toolbox to facilitate engineering of induced neurons with desired patterns of gene expression and related functional properties.
机译：建立神经元身份的转录程序进化为产生在发育过程中顺序出现的丰富的神经元细胞类型多样性。值得注意的是，某些转录因子的瞬时表达也可以赋予非神经细胞神经元的特性。重编程因子与产生神经元身份和多样性的转录网络之间的关系仍然未知。在这里，从598对转录因子的筛选中，我们确定了76对转录因子，它们诱导小鼠成纤维细胞分化为具有神经元特征的细胞。通过比较这些诱导的神经元细胞（iN细胞）与内源性神经元的转录组，我们定义了核心细胞自主神经元的特征。 iN细胞也表现出多样性。每个转录因子对产生具有独特转录模式的iN细胞，可以预测其药理反应。通过将不同的转录因子输入代码链接到定义的转录输出，这项研究描述了神经元同一性和多样性的细胞自治特征，并扩展了重编程工具箱，以促进具有所需基因表达模式和相关功能特性的诱导神经元的工程改造。

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  • 来源
    《Nature》 |2018年第7705期|375-380|共6页
  • 作者

    Tsunemoto Rachel; Lee Sohyon; Sztics Attila; Chubukov Pavel; Sokolova Irina; Blanchard Joel W.; Eadel Kevin T.; Bruggemann Jacob; Wu Chunlei; Torkamani Ali; Sanna Pietro Paolo; Baldwin Kristin K.;

  • 作者单位

    Scripps Res Inst, Dorris Neurosci Ctr, Dept Mol & Cellular Neurosci, La Jolla, CA 92037 USA;

    Scripps Res Inst, Dorris Neurosci Ctr, Dept Mol & Cellular Neurosci, La Jolla, CA 92037 USA;

    Univ Calif San Diego, BioCircuits Inst, La Jolla, CA 92093 USA;

    Scripps Res Inst, Dorris Neurosci Ctr, Dept Mol & Cellular Neurosci, La Jolla, CA 92037 USA;

    Scripps Res Inst, Mol & Integrat Neurosci Dept, La Jolla, CA 92037 USA;

    Scripps Res Inst, Dorris Neurosci Ctr, Dept Mol & Cellular Neurosci, La Jolla, CA 92037 USA;

    Scripps Res Inst, Dorris Neurosci Ctr, Dept Mol & Cellular Neurosci, La Jolla, CA 92037 USA;

    Scripps Res Inst, Integrat Struct & Computat Biol, La Jolla, CA 92037 USA;

    Scripps Res Inst, Integrat Struct & Computat Biol, La Jolla, CA 92037 USA;

    Scripps Hlth, Scripps Translat Sci Inst, La Jolla, CA USA;

    Scripps Res Inst, Mol & Integrat Neurosci Dept, La Jolla, CA 92037 USA;

    Scripps Res Inst, Dorris Neurosci Ctr, Dept Mol & Cellular Neurosci, La Jolla, CA 92037 USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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