A cellular taxonomy of the adult human spinal cord

Archana Yadav; Kaya J E Matson; Li Li; Isabelle Hua; Joana Petrescu; Kristy Kang; Mor R Alkaslasi; Dylan I Lee; Saadia Hasan; Ahmad Galuta; Annemarie Dedek; Sara Ameri; Jessica Parnell; Mohammad M Alshardan; Feras Abbas Qumqumji; Saud M Alhamad; Alick Pingbei Wang; Gaetan Poulen; Nicolas Lonjon; Florence Vachiery-Lahaye; Pallavi Gaur; Mike A Nalls; Yue A Qi; Dragan Maric; Michael E Ward; Michael E Hildebrand; Pierre-Francois Mery; Emmanuel Bourinet; Luc Bauchet; Eve C Tsai; Hemali Phatnani; Claire E Le Pichon; Vilas Menon; Ariel J Levine

doi:10.1016/j.neuron.2023.01.007

A cellular taxonomy of the adult human spinal cord

Neuron. 2023 Feb 1;111(3):328-344.e7. doi: 10.1016/j.neuron.2023.01.007.

Authors

Archana Yadav¹, Kaya J E Matson², Li Li³, Isabelle Hua³, Joana Petrescu⁴, Kristy Kang⁴, Mor R Alkaslasi⁵, Dylan I Lee¹, Saadia Hasan⁶, Ahmad Galuta⁷, Annemarie Dedek⁸, Sara Ameri⁷, Jessica Parnell⁸, Mohammad M Alshardan⁷, Feras Abbas Qumqumji⁷, Saud M Alhamad⁷, Alick Pingbei Wang⁷, Gaetan Poulen⁹, Nicolas Lonjon⁹, Florence Vachiery-Lahaye⁹, Pallavi Gaur¹, Mike A Nalls¹⁰, Yue A Qi¹¹, Dragan Maric¹², Michael E Ward⁶, Michael E Hildebrand¹³, Pierre-Francois Mery¹⁴, Emmanuel Bourinet¹⁴, Luc Bauchet¹⁵, Eve C Tsai⁷, Hemali Phatnani⁴, Claire E Le Pichon¹⁶, Vilas Menon¹⁷, Ariel J Levine¹⁸

Affiliations

¹ Department of Neurology, Center for Translational and Computational Neuroimmunology, Columbia University, New York, NY, USA.
² Spinal Circuits and Plasticity Unit, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA; Johns Hopkins University Department of Biology, Baltimore, MD 21218, USA.
³ Spinal Circuits and Plasticity Unit, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA.
⁴ Department of Neurology, Center for Translational and Computational Neuroimmunology, Columbia University, New York, NY, USA; Center for Genomics of Neurodegenerative Disease, New York Genome Center, New York, NY, USA.
⁵ Unit on the Development of Neurodegeneration, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, USA; Department of Neuroscience, Brown University, Providence, RI, USA.
⁶ Inherited Neurodegenerative Diseases Unit, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA.
⁷ Neuroscience Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
⁸ Neuroscience Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada; Department of Neuroscience, Carleton University, Ottawa, ON, Canada.
⁹ Department of Neurosurgery, Gui de Chauliac Hospital, and Donation and Transplantation Coordination Unit, Montpellier University Medical Center, Montpellier, France.
¹⁰ Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA; Center for Alzheimer's and Related Dementias, National Institutes of Health, Bethesda, MD, USA; Data Tecnica International LLC, Glen Echo, MD, USA.
¹¹ Center for Alzheimer's and Related Dementias, National Institutes of Health, Bethesda, MD, USA.
¹² Flow and Imaging Cytometry Core Facility, National Institute of Neurological Disorders and Stroke; Bethesda, MD, USA.
¹³ Inherited Neurodegenerative Diseases Unit, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA; Neuroscience Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
¹⁴ Institute of Functional Genomics, Montpellier University, CNRS, INSERM, Montpellier, France.
¹⁵ Department of Neurosurgery, Gui de Chauliac Hospital, and Donation and Transplantation Coordination Unit, Montpellier University Medical Center, Montpellier, France; Institute of Functional Genomics, Montpellier University, CNRS, INSERM, Montpellier, France.
¹⁶ Unit on the Development of Neurodegeneration, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, USA.
¹⁷ Department of Neurology, Center for Translational and Computational Neuroimmunology, Columbia University, New York, NY, USA. Electronic address: vm2545@cumc.columbia.edu.
¹⁸ Spinal Circuits and Plasticity Unit, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA. Electronic address: ariel.levine@nih.gov.

Abstract

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.

Keywords: ALS; cell types; human spinal cord; motoneuron; single cell sequencing; spatial transcriptomics.

Published by Elsevier Inc.

Publication types

Research Support, N.I.H., Intramural
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Amyotrophic Lateral Sclerosis* / metabolism
Animals
Humans
Mammals
Models, Animal
Motor Neurons / metabolism
Neuroglia / metabolism
Spinal Cord / metabolism

Abstract

Publication types

MeSH terms

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