SnRNA-seq reveals the heterogeneity of spinal ventral horn and mechanism of motor neuron axon regeneration
Ye Zhu,
Chengcheng Luan,
Leilei Gong,
Yun Gu,
Xinghui Wang,
Hualin Sun,
Zhifeng Chen,
Qiang Zhou,
Chang Liu,
Qi Shan,
Xiaosong Gu,
Songlin Zhou
Affiliations
Ye Zhu
Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin 300000, China
Chengcheng Luan
Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin 300000, China
Leilei Gong
Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, Nantong, Jiangsu 226001, China
Yun Gu
Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, Nantong, Jiangsu 226001, China
Xinghui Wang
Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, Nantong, Jiangsu 226001, China
Hualin Sun
Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, Nantong, Jiangsu 226001, China
Zhifeng Chen
Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, Nantong, Jiangsu 226001, China
Qiang Zhou
Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, Nantong, Jiangsu 226001, China
Chang Liu
Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, Nantong, Jiangsu 226001, China
Qi Shan
Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin 300000, China
Xiaosong Gu
Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin 300000, China; Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, Nantong, Jiangsu 226001, China; Corresponding author
Songlin Zhou
Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, Nantong, Jiangsu 226001, China; Corresponding author
Summary: Spinal motor neurons, the distinctive neurons of the central nervous system, extend into the peripheral nervous system and have outstanding ability of axon regeneration after injury. Here, we explored the heterogeneity of spinal ventral horn cells after rat sciatic nerve crush via single-nuclei RNA sequencing. Interestingly, regeneration mainly occurred in a Sncg+ and Anxa2+ motor neuron subtype (MN2) surrounded by a newly emerged microglia subtype (Mg6) after injury. Subsequently, microglia depletion slowed down the regeneration of sciatic nerve. OPCs were also involved into the regeneration process. Knockdown of Cacna2d2 in vitro and systemic blocking of Cacna2d2 in vivo improved the axon growth ability, hinting us the importance of Ca2+. Ultimately, we proposed three possible phases of motor neuron axon regeneration: preparation stage, early regeneration stage, and regeneration stage. Taken together, our study provided a resource for deciphering the underlying mechanism of motor neuron axon regeneration in a single cell dimension.
