A Cellular Taxonomy of the Adult Human Spinal Cord
Archana Yadav
(1)
,
Kaya J.E. Matson
(2)
,
Li Li
(2)
,
Isabelle Hua
(2)
,
Joana Petrescu
(1)
,
Kristy Kang
(1)
,
Mor Alkaslasi
(2)
,
Dylan Lee
(1)
,
Saadia Hasan
(2)
,
Ahmad Galuta
(3)
,
Annemarie Dedek
(3, 4)
,
Sara Ameri
(3)
,
Jessica Parnell
(3, 4)
,
Mohammad Alshardan
(3)
,
Feras Abbas Qumqumji
(3)
,
Saud Alhamad
(3)
,
Alick Pingbei Wang
(3)
,
Gaetan Poulen
(5)
,
Nicolas Lonjon
(5)
,
Florence Vachiery-Lahaye
(5)
,
Pallavi Gaur
(2)
,
Mike Nalls
(2)
,
Yue Qi
(2)
,
Michael Ward
(2)
,
Michael Hildebrand
(4)
,
Pierre-François Méry
(6)
,
Emmanuel Bourinet
(6)
,
Luc Bauchet
(5, 6)
,
Eve Tsai
(3)
,
Hemali Phatnani
(2)
,
Claire Le Pichon
(2)
,
Vilas Menon
(2)
,
Ariel Levine
(2)
Annemarie Dedek
- Fonction : Auteur
- PersonId : 1154700
- ORCID : 0000-0002-7215-4928
Michael Ward
- Fonction : Auteur
- PersonId : 1154701
- ORCID : 0000-0002-5296-8051
Pierre-François Méry
- Fonction : Auteur
- PersonId : 182507
- IdHAL : pierre-francois-mery
- ORCID : 0000-0001-6214-5422
Emmanuel Bourinet
- Fonction : Auteur
- PersonId : 737053
- IdHAL : emmanuel-bourinet
- ORCID : 0000-0001-8021-0419
- IdRef : 07014415X
Vilas Menon
- Fonction : Auteur
- PersonId : 1154702
- ORCID : 0000-0002-4096-8601
Ariel Levine
- Fonction : Auteur
- PersonId : 1154703
- ORCID : 0000-0002-0335-0730
Résumé
The mammalian spinal cord functions as a community of glial and neuronal cell types to accomplish sensory processing, autonomic control, and movement; conversely, the dysfunction of these cell types following spinal cord injury or disease states can lead to chronic pain, paralysis, and death. While we have made great strides in understanding spinal cellular diversity in animal models, it is crucial to characterize human biology directly to uncover specialized features of basic function and to illuminate 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 observed 29 glial clusters, including rare cell types such as ependymal cells, and 35 neuronal clusters, which we found are organized principally by anatomical location. To demonstrate the potential of this resource for understanding human disease, we analyzed the transcriptome of spinal motoneurons that are prone to degeneration in amyotrophic lateral sclerosis (ALS) and other diseases. We found that, compared with all other spinal neurons, human motoneurons are defined by genes related to cell size, cytoskeletal structure, and ALS, thereby supporting a model of a specialized motoneuron molecular repertoire that underlies their selective vulnerability to disease. We include a publicly available browsable web resource with this work, in the hope that it will catalyze future discoveries about human spinal cord biology.