Summary: Using single nucleus RNA sequencing, researchers have mapped 21 distinct subtypes of motor neurons along the mouse spinal cord.
Source: NIH
Researchers at the National Institutes of Health (NIH) have produced a detailed molecular atlas of motor neurons across the mouse spinal cord, revealing an unexpectedly wide diversity of cell types. The study identifies 21 transcriptionally distinct neuronal subtypes, clarifies their anatomical distribution, and highlights cellular groups that may be particularly relevant to neurodegenerative diseases.
Using a targeted single nucleus RNA sequencing approach, the team created a high-resolution classification of cholinergic neurons—including skeletal motor neurons, visceral motor neurons that control internal organs and glands, and cholinergic interneurons. The resulting atlas provides new markers to distinguish these classes and offers a framework for understanding how specific neuronal subtypes contribute to movement, autonomic function, and disease vulnerability.
The study was led by Claire Le Pichon, Ph.D., head of the Unit on the Development of Neurodegeneration at NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD).
The research appears in Nature Communications.
Spinal cord motor neurons are central to all forms of movement and autonomic control, from voluntary actions such as walking to the involuntary regulation of organ systems. Historically, these neurons have been grouped into three broad types—skeletal motor neurons, visceral motor neurons and interneurons—but growing evidence has suggested further subtypes within these categories. Diseases such as spinal muscular atrophy and amyotrophic lateral sclerosis (ALS) do not affect all motor neurons equally, which has motivated efforts to map neuronal diversity at the molecular level.
The investigators applied single nucleus RNA sequencing to isolate and profile gene expression from nuclei of cholinergic neurons throughout the adult mouse spinal cord. This method enables the detection of cell type–specific transcriptional signatures even from densely packed or otherwise hard-to-dissociate tissues. The analysis revealed 21 clear transcriptomic classes with distinct marker genes and anatomical localizations.
Among the novel findings, the study shows especially pronounced diversity within visceral motor neurons, which mediate autonomic outputs to organs and glands. These visceral motor neurons split into more than a dozen transcriptomic classes that occupy specific, anatomically restricted regions along the spinal axis. The researchers also report greater rostrocaudal extension of some visceral motor populations than previously appreciated, suggesting there are subtypes whose functions remain to be characterized.
Skeletal motor neurons also displayed complex transcriptional structure. The analysis distinguished alpha and gamma motor neuron classes and identified a third skeletal subtype that may correspond to the historically described beta motor neurons, which have been difficult to define molecularly until now.
By providing molecular markers and spatial context for these cell types, the atlas creates opportunities to link specific neuronal populations to their physiological roles and to investigate why particular subtypes are selectively vulnerable in degenerative diseases. Better molecular definitions can guide future studies that model disease, test targeted therapies, or develop biomarkers that reflect the health of defined motor neuron populations.
All data from the study have been made available by the authors for exploration and reuse: http://www.spinalcordatlas.org
About this neuroscience research news
Source: NIH
Contact: Linda Huynh – NIH
Image: The image is in the public domain
Original Research: Open access.
“Single nucleus RNA-sequencing defines unexpected diversity of cholinergic neuron types in the adult mouse spinal cord” by Alkaslasi MR, Piccus ZE, Hareendran S, Silberberg H, Chen L, Zhang Y, Petros TJ, and Le Pichon CE. Nature Communications
Abstract
Single nucleus RNA-sequencing defines unexpected diversity of cholinergic neuron types in the adult mouse spinal cord
In vertebrates, motor control depends on cholinergic neurons of the spinal cord, a population that has been studied for more than a century. Despite this long history, the full heterogeneity of these neurons and their distinct roles in the adult nervous system have not been fully defined.
Here, the authors developed a targeted single nucleus RNA sequencing strategy and applied it to identify an array of cholinergic interneurons, visceral motor neurons, and skeletal motor neurons. Their data reveal marker genes that distinguish these classes and expose pronounced diversity within each group.
Specifically, visceral motor neurons, which govern autonomic functions, can be subdivided into more than a dozen transcriptomic classes with anatomically restricted distributions along the spinal cord. The skeletal motor neuron population likewise shows complex organization, with alpha and gamma motor neurons clearly separable and a third molecularly distinct subtype that may correspond to beta motor neurons.
Together, these results provide a comprehensive transcriptomic description of spinal cholinergic neurons—cellular substrates essential for movement and autonomic physiology and relevant to degenerative disorders that selectively affect motor neuron subtypes.