Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Department of Neuroscience, Brown University, Providence, RI, USA.
Nat Commun. 2021 Apr 30;12(1):2471. doi: 10.1038/s41467-021-22691-2.
In vertebrates, motor control relies on cholinergic neurons in the spinal cord that have been extensively studied over the past hundred years, yet the full heterogeneity of these neurons and their different functional roles in the adult remain to be defined. Here, we develop a targeted single nuclear RNA sequencing approach and use it to identify an array of cholinergic interneurons, visceral and skeletal motor neurons. Our data expose markers for distinguishing these classes of cholinergic neurons and their rich diversity. Specifically, visceral motor neurons, which provide autonomic control, can be divided into more than a dozen transcriptomic classes with anatomically restricted localization along the spinal cord. The complexity of the skeletal motor neurons is also reflected in our analysis with alpha, gamma, and a third subtype, possibly corresponding to the elusive beta motor neurons, clearly distinguished. In combination, our data provide a comprehensive transcriptomic description of this important population of neurons that control many aspects of physiology and movement and encompass the cellular substrates for debilitating degenerative disorders.
在脊椎动物中，运动控制依赖于脊髓中的胆碱能神经元，在过去的一百年中，这些神经元已经得到了广泛的研究，但这些神经元的完全异质性及其在成年期的不同功能作用仍有待确定。在这里，我们开发了一种靶向性的单个核 RNA 测序方法，并利用它来鉴定一系列胆碱能中间神经元、内脏和骨骼运动神经元。我们的数据揭示了区分这些胆碱能神经元及其丰富多样性的标记物。具体来说，提供自主控制的内脏运动神经元可以分为十几个转录组类，它们在脊髓中沿着特定的解剖位置定位。我们的分析还反映了骨骼运动神经元的复杂性，其中 alpha、gamma 和第三种亚型可以明显区分，可能对应于难以捉摸的 beta 运动神经元。综合来看，我们的数据提供了对这一重要神经元群体的全面转录组描述，这些神经元控制着生理学和运动的许多方面，并包含了导致衰弱退行性疾病的细胞基础。
