GEO series

A multi-omics characterization of the human lumbar spinal cord and motor cortex reveals non-overlapping molecular signatures in ALS [snRNA-Seq; snATAC-Seq]

GSE330130 Homo sapiens Genome binding/occupancy profiling by high throughput sequencing; Expression profiling by high throughput sequencing 87 samples Submitted 2026/07/24 Platform GPL34281

Summary

Amyotrophic lateral sclerosis (ALS) is a debilitating neurodegenerative disease characterized by the loss of upper and lower motor neurons in the motor cortex (MTC) and spinal cord (SC), respectively, leading to muscle atrophy and ultimately respiratory failure. While motor neurons (MNs) are the selectively vulnerable cell type, their interactions with glia contribute to the progression of ALS pathology. However, it remains unclear whether the molecular alterations underlying MN and glial dysfunction in ALS are the same in the MTC and lumbar SC (LSC). To address this, we constructed spatially-resolved gene expression maps of the MTC and LSC by combining spatial and single-nucleus transcriptomic profiles from a cohort of non-neurological controls and ALS patients clinically stratified by site of symptom onset. In the ventral horn of the LSC, we see a decrease in genes associated with MNs and synaptic signaling in ALS patients. We also identify region-specific alterations in endothelial- and glial-related functions. Notably, the severity of these MN deficits and endothelial-related functions is influenced by the site of symptom onset, whereas alterations in glial function largely are not. In the MTC, we observe layer-specific increases in synaptic signaling in ALS patients. Comparing the molecular and cellular changes within the LSC and MTC in ALS indicates that they are predominantly non-overlapping, and have different molecular signatures.

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Direct links to NCBI, no account and no request form: the whole study as GSE330130_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 87 samples. Raw sequencing reads are also available from ENA.

Whole study · RAW.tar ↓ Series matrix ↓ All supplementary files ↗ Raw reads on ENA ↗

Also filed as BioProject PRJNA1462802 and SRA study SRP698107. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Study design

40 conditions, each sampled once — no replicated groups

Read from the first 40 of 87 sample titles: 40 distinct titles with little repetition. Check it against the sample list below before relying on it.

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