Cited by 210Single-cell and spatial transcriptomicsNeuroscience and Neuropharmacology ResearchDevelopmental Biology and Gene Regulation

Single-cell transcriptomic analysis of the adult mouse spinal cord reveals molecular diversity of autonomic and skeletal motor neurons

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Blum, Jacob A., Klemm, Sandy, Shadrach, Jennifer L., Guttenplan, Kevin A., Nakayama, Lisa, Kathiria, Arwa, Hoang, Phuong T., Gautier, Olivia +3 more·2021·Nature Neuroscience

Abstract

The spinal cord is a fascinating structure that is responsible for coordinating movement in vertebrates. Spinal motor neurons control muscle activity by transmitting signals from the spinal cord to diverse peripheral targets. In this study, we profiled 43,890 single-nucleus transcriptomes from the adult mouse spinal cord using fluorescence-activated nuclei sorting to enrich for motor neuron nuclei. We identified 16 sympathetic motor neuron clusters, which are distinguishable by spatial localization and expression of neuromodulatory signaling genes. We found surprising skeletal motor neuron heterogeneity in the adult spinal cord, including transcriptional differences that correlate with electrophysiologically and spatially distinct motor pools. We also provide evidence for a novel transcriptional subpopulation of skeletal motor neuron (γ*). Collectively, these data provide a single-cell transcriptional atlas ( http://spinalcordatlas.org ) for investigating the organizing molecular logic of adult motor neuron diversity, as well as the cellular and molecular basis of motor neuron function in health and disease.

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  • Digit-innervating motoneurons expressing Cpne4 and Fign separated into two subtypes, one found in limb-innervating regions (cervical and lumbar) and one specifically localized to the lumbar spinal cord.

    “For example, we found that digit-innervating motoneurons, expressing Cpne4 and Fign38, separated into two subtypes, one found in limb-innervating regions (both cervical and lumbar) and one that was specifically localized to the lumbar spinal cord39,40”

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  1. [31]Kaplan A Neuronal matrix Metalloproteinase-9 is a determinant of selective Neurodegeneration. Neuron 81, 333– 348 (2014). 24462097 PMC6015650

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Authors
Blum, J. A., Klemm, S., Shadrach, J. L., Guttenplan, K. A., Nakayama, L., Kathiria, A., Hoang, P. T., Gautier, O., Kaltschmidt, J. A., Greenleaf, W. J., & Gitler, A. D.
Affiliations
  • Stanford Medicine (US)
  • Chan Zuckerberg Biohub San Francisco (US)
Corresponding author
Gitler, Aaron D.
Venue
Nature Neuroscience
Published
2021-02-15
Volume
24
Issue
4
Pages
572-583
ISSN
  • 1097-6256 (ISSN-L)
  • 1546-1726
OpenAlex
W3130700305
Cited by
210
References
53
Citations by year
2026: 29 · 2025: 38 · 2024: 33 · 2023: 50 · 2022: 40 · 2021: 19 · 2020: 1
FWCI
11.15
Type
journal article
Language
en
Open access
Locations
  • Nature Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
U.S. Department of Health & Human Services | National Institutes of Health (R35NS097263, R01NS083998)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords
spinal motoneurons, gamma motor neurons, motor pools, transcriptional atlas, single-nucleus transcriptomics, mice
MeSH terms
Animals, Autonomic Nervous System, Motor Neurons, Spinal Cord, Viscera, Muscle, Skeletal, Mice, Single-Cell Analysis, Transcriptome

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