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Embryonic motor neuron programming factors reactivate immature gene expression and suppress ALS pathologies in postnatal motor neurons

GSE261314 Mus musculus Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing 4 samples Submitted 2025/06/15 Platform GPL19057Platform GPL24247
Summary
Aging is a major risk factor in amyotrophic lateral sclerosis (ALS) and other adult-onset neurodegenerative disorders. Whereas young neurons are capable of buffering disease-causing stresses, mature neurons lose this ability and degenerate over time. We hypothesized that the resilience of young motor neurons could be restored by re-expression of the embryonic motor neuron selector transcription factors ISL1 and LHX3. We found that viral re-expression of ISL1 and LHX3 reactivates aspects of the youthful gene expression program in mature motor neurons and alleviates key disease-relevant phenotypes in the SOD1G93A mouse model of ALS. Our results suggest that redeployment of lineage-specific neuronal selector transcription factors can be an effective strategy to attenuate age-dependent phenotypes in neurodegenerative disease.
Published in
Embryonic motor neuron programming factors reactivate immature gene expression and suppress ALS pathologies in postnatal motor neurons
Lowry ER, Patel T, Costa JA et al. · Nature neuroscience 2025 · PMID 40796666 · doi:10.1038/s41593-025-02033-x
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Also filed as BioProject PRJNA1086476 and SRA study SRP494541. Searching any of these in the dataset finder brings you back here.

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