Peripheral Nerve Single-Cell Analysis Identifies Mesenchymal Ligands that Promote Axonal Growth
Peripheral Nerve Single-Cell Analysis Identifies Mesenchymal Ligands that Promote Axonal Growth
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DOI：
10.1523/eneuro.0066-20.2020
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发表时间：
2020-04
期刊：
影响因子：
3.4
通讯作者：
Jeremy S. Toma;Konstantina Karamboulas;Matthew J. Carr;Adelaida Kolaj;S. Yuzwa;N. Mahmud;M. Storer;D. Kaplan;F. Miller
中科院分区：
文献类型：
--
作者：
Jeremy S. Toma;Konstantina Karamboulas;Matthew J. Carr;Adelaida Kolaj;S. Yuzwa;N. Mahmud;M. Storer;D. Kaplan;F. Miller
摘要周围神经为轴突的发育和再生提供了良好的生长环境，对许多非神经组织的维持和修复是必不可少的。这种能力在很大程度上归因于神经驻留的雪旺细胞分泌的旁分泌因子。在这里，我们使用单细胞转录图谱来识别不同受损的啮齿动物神经细胞类型所产生的配体，并将其与细胞表面质谱学相结合，以计算模型潜在的旁分泌与周围神经元的相互作用。这些分析表明，外周神经使许多配体被预测作用于外周和中枢神经系统神经元，包括已知的和以前未描述的配体。虽然雪旺细胞是受损神经中重要的配体来源，但超过一半的预测配体是由神经驻留的间充质细胞组成的，包括与周围轴突关系最密切的神经内神经细胞。至少有三种间充质配体，ANGPT1，CCL11和VEGFC，当局部应用于交感神经轴突时，促进生长。因此，这些数据确定了神经间充质细胞意想不到的旁分泌作用，并表明多种细胞类型有助于为外周轴突创造高度促进生长的环境。
Abstract Peripheral nerves provide a supportive growth environment for developing and regenerating axons and are essential for maintenance and repair of many non-neural tissues. This capacity has largely been ascribed to paracrine factors secreted by nerve-resident Schwann cells. Here, we used single-cell transcriptional profiling to identify ligands made by different injured rodent nerve cell types and have combined this with cell-surface mass spectrometry to computationally model potential paracrine interactions with peripheral neurons. These analyses show that peripheral nerves make many ligands predicted to act on peripheral and CNS neurons, including known and previously uncharacterized ligands. While Schwann cells are an important ligand source within injured nerves, more than half of the predicted ligands are made by nerve-resident mesenchymal cells, including the endoneurial cells most closely associated with peripheral axons. At least three of these mesenchymal ligands, ANGPT1, CCL11, and VEGFC, promote growth when locally applied on sympathetic axons. These data therefore identify an unexpected paracrine role for nerve mesenchymal cells and suggest that multiple cell types contribute to creating a highly pro-growth environment for peripheral axons.