小柯机器人

损伤的成年神经元能够退化为胚胎转录生长状态
2020-04-18 09:53

近日,美国加州大学圣地亚哥分析Mark H. Tuszynski、Gunnar H. D. Poplawski等研究人员合作发现,损伤的成年神经元能够退化为胚胎转录生长状态。相关论文于2020年4月15日在线发表于国际学术期刊《自然》。

研究人员对小鼠的皮质脊髓束(CST)运动神经元进行翻译谱分析,以鉴定脊髓损伤和脊髓来源神经祖细胞(NPC)移植后它们的“再生转录组”。值得注意的是,单独的损伤和与NPC移植相结合的损伤在宿主CST神经元中引起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。再生转录组代表了对CST神经元胚胎转录状态的修改。亨廷顿基因(Htt)是再生转录组中的中心枢纽。Htt的缺失显著减弱了再生,这表明Htt在损伤后在神经可塑性中具有关键作用。
 
据悉,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。然而,再生的分子机制尚不清楚。
 
附:英文原文

Title: Injured adult neurons regress to an embryonic transcriptional growth state

Author: Gunnar H. D. Poplawski, Riki Kawaguchi, Erna Van Niekerk, Paul Lu, Neil Mehta, Philip Canete, Richard Lie, Ioannis Dragatsis, Jessica M. Meves, Binhai Zheng, Giovanni Coppola, Mark H. Tuszynski

Issue&Volume: 2020-04-15

Abstract: Grafts of spinal-cord-derived neural progenitor cells (NPCs) enable the robust regeneration of corticospinal axons and restore forelimb function after spinal cord injury1; 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.

DOI: 10.1038/s41586-020-2200-5

Source: https://www.nature.com/articles/s41586-020-2200-5

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

分享到:

0