Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University Medical Center, New York, NY, USA.
Columbia University Motor Neuron Center, Columbia University Medical Center, New York, NY, USA.
Nat Commun. 2021 Mar 1;12(1):1451. doi: 10.1038/s41467-021-21880-3.
Proprioceptive feedback mainly derives from groups Ia and II muscle spindle (MS) afferents and group Ib Golgi tendon organ (GTO) afferents, but the molecular correlates of these three afferent subtypes remain unknown. We performed single cell RNA sequencing of genetically identified adult proprioceptors and uncovered five molecularly distinct neuronal clusters. Validation of cluster-specific transcripts in dorsal root ganglia and skeletal muscle demonstrates that two of these clusters correspond to group Ia MS afferents and group Ib GTO afferent proprioceptors, respectively, and suggest that the remaining clusters could represent group II MS afferents. Lineage analysis between proprioceptor transcriptomes at different developmental stages provides evidence that proprioceptor subtype identities emerge late in development. Together, our data provide comprehensive molecular signatures for groups Ia and II MS afferents and group Ib GTO afferents, enabling genetic interrogation of the role of individual proprioceptor subtypes in regulating motor output.
本体感受反馈主要来自 Ia 群和 II 群肌梭（MS）传入纤维和 Ib 群高尔基腱器官（GTO）传入纤维，但这三种传入纤维亚型的分子相关性尚不清楚。我们对遗传鉴定的成年本体感受器进行了单细胞 RNA 测序，揭示了五个分子上不同的神经元簇。在背根神经节和骨骼肌中对簇特异性转录本的验证表明，其中两个簇分别对应 Ia 群 MS 传入纤维和 Ib 群 GTO 传入本体感受器，并且提示其余簇可能代表 II 群 MS 传入纤维。在不同发育阶段的本体感受器转录组之间进行的谱系分析提供了证据，表明本体感受器亚型的身份在发育后期出现。总之，我们的数据为 Ia 群和 II 群 MS 传入纤维和 Ib 群 GTO 传入纤维提供了全面的分子特征，使我们能够通过遗传手段研究单个本体感受器亚型在调节运动输出中的作用。
