Summary: Study links motor neurons’ large cell size and supporting structures with genes that underly vulnerability to degeneration associated with ALS.
New research offers clues about the biology of cells in the spinal cord that die off in amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases.
A team of researchers supported by the National Institutes of Health has found evidence linking motor neurons’ large cell size and supporting structure with the genes that underlie their vulnerability to degeneration in ALS.
Findings appeared in Neuron.
The study resulted in a catalog (or “atlas”) characterizing the diverse community of cell types within the human spinal cord. By examining gene expression at the single-cell level, the researchers identified dozens of cell types in the spinal cord and analyzed their molecular profiles.
They demonstrated the usefulness of the atlas by looking closely at motor neurons, which provide voluntary movement and motor control. Motor neurons, which degenerate and die in ALS, are large cells with one long extension called an axon―up to a meter long―that conducts signals from the spinal cord to the muscle fiber.
The team found that motor neurons are distinguished by a set of genes that may enable the large size of the motor neuron cell body and lengthy axon, but also underlie their vulnerability to degeneration. Their molecular profile was defined by genes involved in cytoskeletal structure, which gives the cell shape and organizes the structures within; neurofilament genes related to cell size; and genes linked to the onset of ALS.
Additional experiments showed that ALS-related genes are also enriched in motor neurons in mice. With these findings taken together, the study gives insight into ALS and demonstrates the utility of the spinal cell atlas for studying disease and possible interventions.
About this ALS research news
Author: Press Office Source: NIH Contact: Press Office – NIH Image: The image is in the public domain
A cellular taxonomy of the adult human spinal cord
Single-nucleus RNA sequencing and spatial transcriptomics of adult human spinal cord
Glial classes include proliferative microglia and white and gray matter astrocytes
Dorsal neuron types are more discrete and ventral neuron groups are more overlapping
The human motoneuron transcriptional profile is enriched for genes related to ALS
The mammalian spinal cord functions as a community of cell types for sensory processing, autonomic control, and movement. While animal models have advanced our understanding of spinal cellular diversity, characterizing human biology directly is important to uncover specialized features of basic function and human pathology.
Here, we present a cellular taxonomy of the adult human spinal cord using single-nucleus RNA sequencing with spatial transcriptomics and antibody validation.
We identified 29 glial clusters and 35 neuronal clusters, organized principally by anatomical location. To demonstrate the relevance of this resource to human disease, we analyzed spinal motoneurons, which degenerate in amyotrophic lateral sclerosis (ALS) and other diseases.
We found that compared with other spinal neurons, human motoneurons are defined by genes related to cell size, cytoskeletal structure, and ALS, suggesting a specialized molecular repertoire underlying their selective vulnerability.
We include a web resource to facilitate further investigations into human spinal cord biology.