GEO series

Myeloid C3 causes neuronal injury prior to synapse loss [snMulti-ome-seq]

GSE260978 Mus musculus Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing 8 samples Submitted 2025/02/14 Platform GPL24247

Summary

Complement component C3 mediates pathology in several CNS neurodegenerative diseases, but the cellular and molecular mechanisms leading to neuronal injury remain unclear. Herein, we examined how C3 deletion affects glial profiles and anterior visual pathway pathology in an animal model of neuroinflammation. scRNA-seq from mouse brain and optic nerve revealed that C3 expression defined disease-associated glial subtypes which were characterized by increased mTOR activation, cell metabolism, and translation. Deletion of C3 restored these glia towards homeostatic profiles. Myeloid-derived C3 mediated injury in optic nerve axons and retinal ganglion cells (RGCs) at the peak of EAE. To elucidate the timing of pathology we examined retinas prior to symptom onset and found reductions in Brn3a, an RGC transcription factor involved in dendritic arborization and protection from apoptosis. Our study supports a direct role for C3 in activating the mTOR-ribosomal biogenesis axis in glia which subsequently mediate early neuro-axonal stress and later synapse loss.

Published in

Myeloid lineage C3 induces reactive gliosis and neuronal stress during CNS inflammation

Garton T, Smith MD, Kesharwani A et al. · Nature communications 2025 · PMID 40216817 · doi:10.1038/s41467-025-58708-3

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Direct links to NCBI, no account and no request form: the whole study as GSE260978_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 8 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 PRJNA1084767 and SRA study SRP493644. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40216817) ↗

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