biostudies-literatureYadav AIntramural NIH HHSNIA NIH HHSNINDS NIH HHS328-344.e7https://www.ebi.ac.uk/biostudies/studies/S-EPMC10044516biostudies-literatureUnknown111(3)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.NeuronA cellular taxonomy of the adult human spinal cord.PMC10044516U54 AG076040ZIA NS003155R01 NS116350U01 AG016976ZIA HD008966ZIA NS003153R01 AG066831Maric DPetrescu JPhatnani HAlshardan MMLonjon NQumqumji FAWang APLe Pichon CEHua IParnell JMenon VHasan SLee DIQi YALevine AJTsai ECDedek AKang KHildebrand MEMery PFAlkaslasi MRWard MEVachiery-Lahaye FYadav ALi LAlhamad SMGaur PGaluta ABourinet EMatson KJEAmeri SPoulen GNalls MABauchet LfalseA cellular taxonomy of the adult human spinal cord.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.2023-01-01T00:00:00Z2023 Feb2024-11-05T20:48:32.079Z2024-11-05T20:48:32.079ZS-EPMC100445163673142910.1016/j.neuron.2023.01.007