Zhang Yu, Xu Lian, Li Xiaodi, Chen Zhifeng, Chen Jing, Zhang Tao, Gu Xiaosong, Yang Jian
School of Medicine and Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210000, 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 226001, China.
iScience. 2022 Aug 11;25(9):104917. doi: 10.1016/j.isci.2022.104917. eCollection 2022 Sep 16.
Robust axon regeneration of motoneurons (MNs) occurs in rodent models upon peripheral nerve injury (PNI). However, genome-wide dynamic molecules and permissive microenvironment following insult in MNs remain largely unknown. Here, we firstly tackled by high-coverage and massive sequencing of laser-dissected individual ChAT cells to uncover molecules and pro-regenerative programs of MNs from injury to the regenerating phase after PNI. "Injured" populations at 1d∼7d were well distinguished and three response phases were well defined by elucidating with several clues (, etc). We found remarkable changes of genes expressed by injured motoneurons to activate and enhance intrinsic axon regrowth or crosstalk with other cellular or non-cellular counterpart in the activated regenerative microenvironment, specifically microglia/macrophage. We also identified an injury and regeneration-associated module and critical regulators including core transcription factors (, , , , , , and ). This study provides a vital resource and critical molecules for studying neural repair of axotomized motoneurons.
在啮齿动物模型中，周围神经损伤（PNI）后运动神经元（MNs）会发生强大的轴突再生。然而，MNs损伤后全基因组范围内的动态分子和允许性微环境仍 largely未知。在这里，我们首先通过对激光切割的单个ChAT细胞进行高覆盖度和大规模测序，以揭示PNI后从损伤到再生阶段MNs的分子和促再生程序。通过若干线索（，等）阐明，1d至7d的“损伤”群体得到了很好的区分，并且定义了三个反应阶段。我们发现，损伤的运动神经元表达的基因发生了显著变化，以激活和增强内在轴突再生，或在激活的再生微环境中与其他细胞或非细胞对应物发生串扰，特别是小胶质细胞/巨噬细胞。我们还鉴定了一个损伤和再生相关模块以及关键调节因子，包括核心转录因子（，，，，，，和）。这项研究为研究轴突切断的运动神经元的神经修复提供了重要资源和关键分子。
