Summary: Using single nucleus RNA sequencing, researchers have mapped 21 subtypes of motor neurons in the spinal cords of mice.
In a mouse study, National Institutes of Health researchers have identified and mapped a diverse spectrum of motor neurons along the spinal cord. These neurons, which send and receive messages throughout the body, include a subset that is susceptible to neurodegenerative diseases.
Created with a genetic sequencing technique, the atlas reveals 21 subtypes of neurons in discrete areas throughout the spinal cord and offers insight into how these neurons control movement, how they contribute to the functioning of organ systems and why some are disproportionately affected in neurodegenerative diseases.
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).
It appears in Nature Communications.
Spinal cord neurons are responsible for all types of movement in the body, ranging from voluntary movements like walking to the involuntary constriction and relaxation of the stomach as it processes its contents. Traditionally, scientists categorize these neurons into three main types: skeletal motor neurons, visceral motor neurons and interneurons.
Previous research suggests there are additional subtypes within these three categories and that some of these subtypes may be more vulnerable to neurodegenerative diseases than others. For example, diseases like spinal muscular atrophy and amyotrophic lateral sclerosis, or ALS, affect only certain types of skeletal muscle neurons.
In the current study, the team used a technique called single nucleus RNA sequencing to identify 21 subtypes of spinal cord neurons in mice. The findings reveal highly distinct subtypes, especially among motor neurons that control the glands and internal organs. The team also discovered that visceral motor neurons extend higher up along the spinal column than previously known. The authors believe these motor neurons may be newly discovered subtypes with unknown functions.
Single nucleus RNA-sequencing defines unexpected diversity of cholinergic neuron types in the adult mouse spinal cord
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.