Challenges of profiling motor neuron transcriptomes from human spinal cord

Single-nucleus RNA sequencing (snRNA-seq) is a powerful approach to study cellular heterogeneity within and across tissues. We and others have previously performed snRNA-seq on adult mouse spinal cord. 1 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. Single-cell transcriptomic analysis of the adult mouse spinal cord reveals molecular diversity of autonomic and skeletal motor neurons. Nat. Neurosci. 2021; 24: 572-583 Crossref PubMed Scopus (78) Google Scholar ,2 Alkaslasi M.R. Piccus Z.E. Hareendran S. Silberberg H. Chen L. Zhang Y. Petros T.J. Le Pichon C.E. Single nucleus RNA-sequencing defines unexpected diversity of cholinergic neuron types in the adult mouse spinal cord. Nat. Commun. 2021; 12: 2471https://doi.org/10.1038/s41467-021-22691-2 Crossref PubMed Scopus (45) Google Scholar To begin to investigate human motor neurons, we performed a pilot snRNA-seq experiment on adult human spinal cord and found discrepancies with Yadav et al., who recently performed snRNA-seq on human spinal cord. 3 Yadav A. Matson K.J.E. Li L. Hua I. Petrescu J. Kang K. Alkaslasi M.R. Lee D.I. Hasan S. Galuta A. et al. A cellular taxonomy of the adult human spinal cord. Neuron. 2023; 111: 328-344.e7https://doi.org/10.1016/j.neuron.2023.01.007 Abstract Full Text Full Text PDF PubMed Scopus (17) Google Scholar A cellular taxonomy of the adult human spinal cordYadav et al.NeuronFebruary 01, 2023In BriefYadav, Matson, et al. use single-nucleus RNA sequencing, spatial transcriptomics, and immunohistochemistry to profile the cell types of the adult human spinal cord, identifying 64 glial and neuronal populations. This resource reveals how the unique molecular environments of specific cell types could contribute to chronic pain or neurodegeneration. Full-Text PDF Open AccessA reproducible signature of cytoskeletal and ALS-related genes in human motoneuronsYadav et al.NeuronDecember 06, 2023In BriefWe recently created an atlas of the adult human lumbar spinal cord.1 As part of this work, we found that motoneurons are distinguished by gene expression related to cytoskeletal structure, cell size, and amyotrophic lateral sclerosis (ALS). We observed this pattern through single-nucleus RNA sequencing (snRNA-seq) (seven donors), validated it with spatial transcriptomics (five donors), and demonstrated it at the protein level for several key factors (four donors). Full-Text PDF