A fine-grained atlas of 360,392 nuclei resolving how amyotrophic lateral sclerosis selectively endangers neurons across the human cortical motor circuit — and the convergent molecular program they share.
Figure 1Pooled snRNA-seq with Souporcell demultiplexing and bulk RNA-seq were integrated via scVI into an atlas of 72 subtypes across 28 donors. Downstream analyses resolved selectively vulnerable cell types, spatial localisation (cell2location), and a shared cross-cell-type vulnerability signature spanning the upper motor circuit.
Seventy-two transcriptomic subtypes across six major cell classes, sampled from a sex-balanced cohort of 28 donors.
Fig. 4The six major cell classes resolved into 72 fine-grained subtypes, integrated with scVI and validated spatially with cell2location.
All datasets, figures and analysis notebooks are openly available. Download the processed objects, browse the cells interactively, or reproduce the analysis end to end.
1Wellcome Sanger Institute, Hinxton, UK
2Gene Lay Institute of Immunology and Inflammation, Brigham and Women's Hospital & Harvard Medical School, Boston, MA, USA
3EMBL — European Bioinformatics Institute, Wellcome Genome Campus, Cambridge, UK
4Department of Basic and Clinical Neuroscience, IoPPN, King's College London, UK
5London Neurodegenerative Diseases Brain Bank, IoPPN, King's College London, UK
6John van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, UK
7Wellcome–MRC Cambridge Stem Cell Institute, University of Cambridge, UK