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Sci Rep. 2016 Aug 25;6:31851. doi: 10.1038/srep31851.

Single-cell RNA-seq reveals distinct injury responses in different types of DRG sensory neurons.

Hu G1,2,3, Huang K2, Hu Y2,3, Du G2, Xue Z3, Zhu X1,4, Fan G1,2,5.

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School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles CA 90095, USA.
Translational Center for Stem Cell Research, Tongji Hospital, Department of Regenerative Medicine, Tongji University School of Medicine, Shanghai 20065, China.
Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China.
Wuxi Medical School, Jiangnan University, Wuxi City, Jiangsu Province, China.


Peripheral nerve injury leads to various injury-induced responses in sensory neurons including physiological pain, neuronal cell death, and nerve regeneration. In this study, we performed single-cell RNA-sequencing (scRNA-seq) analysis of mouse nonpeptidergic nociceptors (NP), peptidergic nociceptors (PEP), and large myelinated sensory neurons (LM) under both control and injury conditions at 3 days after sciatic nerve transection (SNT). After performing principle component and weighted gene co-expression network analysis, we categorized dorsal root ganglion (DRG) neurons into different subtypes and discovered co-regulated injury-response genes including novel regeneration associated genes (RAGs) in association with neuronal development, protein translation and cytoplasm transportation. In addition, we found significant up-regulation of the genes associated with cell death such as Pdcd2 in a subset of NP neurons after axotomy, implicating their actions in neuronal cell death upon nerve injury. Our study revealed the distinctive and sustained heterogeneity of transcriptomic responses to injury at single neuron level, implicating the involvement of different gene regulatory networks in nerve regeneration, neuronal cell death and neuropathy in different population of DRG neurons.

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