Transcriptional Reprogramming of Distinct Peripheral Sensory Neuron Subtypes after Axonal Injury.
Transcriptional Reprogramming of Distinct Peripheral Sensory Neuron Subtypes after Axonal Injury.
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轴突损伤后独特的周围感觉神经元亚型的转录重编程。
DOI：
10.1016/j.neuron.2020.07.026
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发表时间：
2020-10-14
期刊：
影响因子：
16.2
通讯作者：
Woolf CJ
中科院分区：
文献类型：
--
作者：
Renthal W;Tochitsky I;Yang L;Cheng YC;Li E;Kawaguchi R;Geschwind DH;Woolf CJ
初级躯体感觉神经元通过细胞大小、髓鞘形成以及不同受体和离子通道的表达的差异来专门传递特定类型的感觉信息，这些差异共同定义了它们的转录和功能身份。通过在单细胞分辨率下分析感觉神经节，我们发现所有体感神经元亚型对周围神经损伤都有类似的转录反应，既促进轴突再生又抑制细胞身份。在非神经元细胞中未观察到的这种转录重编程在与靶神经再支配相似的时间过程中消退，并且与原始细胞身份的恢复相关。损伤诱导的转录重编程需要ATF 3，这是一种在损伤后快速诱导的转录因子，并且是轴突再生和功能恢复所必需的。我们的研究结果表明，周围神经损伤后早期诱导的转录因子可能赋予感觉神经元转化为再生状态所需的细胞可塑性。背根神经节神经元在周围神经系统中传递躯体感觉和疼痛刺激。在本期《神经元》杂志中，Renthal等人（2020）描述了外周神经损伤后神经元亚型之间诱导的转录程序，这是神经再生所必需的。
Primary somatosensory neurons are specialized to transmit specific types of sensory information through differences in cell size, myelination, and the expression of distinct receptors and ion channels, which together define their transcriptional and functional identity. By profiling sensory ganglia at single-cell resolution, we find that the all somatosensory neuronal subtypes undergo a similar transcriptional response to peripheral nerve injury that both promotes axonal regeneration and suppresses cell identity. This transcriptional reprogramming, which is not observed in non-neuronal cells, resolves over a similar time course as target reinnervation and is associated with the restoration of original cell identity. Injury-induced transcriptional reprogramming requires ATF3, a transcription factor which is induced rapidly after injury and necessary for axonal regeneration and functional recovery. Our findings suggest that transcription factors induced early after peripheral nerve injury likely confer the cellular plasticity required for sensory neurons to transform into a regenerative state. Dorsal root ganglion neurons transduce somatosensory and painful stimuli in the peripheral nervous system. In this issue of Neuron, Renthal et al. (2020), characterize a transcriptional program induced across neuronal subtypes after peripheral nerve injury that is necessary for nerve regeneration.
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