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首页> 外文期刊>Nature >Injured adult neurons regress to an embryonic transcriptional growth state
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Injured adult neurons regress to an embryonic transcriptional growth state

机译：受伤的成年神经元退化为胚胎转录生长状态

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摘要

Grafts of spinal-cord-derived neural progenitor cells (NPCs) enable the robust regeneration of corticospinal axons and restore forelimb function after spinal cord injury(1); however, the molecular mechanisms that underlie this regeneration are unknown. Here we perform translational profiling specifically of corticospinal tract (CST) motor neurons in mice, to identify their 'regenerative transcriptome' after spinal cord injury and NPC grafting. Notably, both injury alone and injury combined with NPC grafts elicit virtually identical early transcriptomic responses in host CST neurons. However, in mice with injury alone this regenerative transcriptome is downregulated after two weeks, whereas in NPC-grafted mice this transcriptome is sustained. The regenerative transcriptome represents a reversion to an embryonic transcriptional state of the CST neuron. The huntingtin gene (Htt) is a central hub in the regeneration transcriptome; deletion of Htt significantly attenuates regeneration, which shows that Htt has a key role in neural plasticity after injury.In mouse models of central nervous system injury, Htt is shown to be a key component of the regulatory program associated with reversion of the neuronal transcriptome to a less-mature state.
机译：脊髓源性神经祖细胞（NPC）的移植能够使脊髓损伤后的皮质脊髓轴突再生并恢复前肢功能（1）;然而，这种再生的分子机制尚不清楚。在这里，我们对小鼠的皮质脊髓束（CST）运动神经元进行翻译分析，以鉴定脊髓损伤和NPC移植后它们的“再生转录组”。值得注意的是，单独的伤害和与NPC移植的伤害都在宿主CST神经元中引起了几乎相同的早期转录组反应。但是，仅在受伤的小鼠中，该再生转录组在两周后被下调，而在NPC移植的小鼠中，该转录组得以维持。再生转录组代表CST神经元的胚胎转录状态的回复。亨廷顿基因（Htt）是再生转录组中的中心枢纽。 Htt的缺失显着减弱了再生，这表明Htt在损伤后的神经可塑性中具有关键作用。在中枢神经系统损伤的小鼠模型中，Htt被证明是与神经元转录组还原为相关的调节程序的关键成分。一个不太成熟的状态。

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    《Nature》 |2020年第7806期|77-82|共6页
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    Univ Calif San Diego Dept Neurosci La Jolla CA 92093 USA;

    Univ Calif Los Angeles Dept Psychiat Los Angeles CA USA|Univ Calif Los Angeles Dept Neurol Los Angeles CA 90024 USA;

    Univ Calif San Diego Dept Neurosci La Jolla CA 92093 USA|Vet Adm Med Ctr 3350 La Jolla Village Dr San Diego CA 92161 USA;

    Univ Tennessee Dept Physiol Memphis TN 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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