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Transplantation of human glial progenitor cells into adult Huntington Disease mice rescues neuronal architecture and aspects of behavior

GSE211986 Mus musculus Expression profiling by high throughput sequencing 6 samples Submitted 2025/11/20 Platform GPL24247
Summary
Glial pathology is a significant contributor to disease pathogenesis in Huntington disease (HD), and neonatal glial replacement can delay disease progression and rescue aspects of behavior in mouse models of HD. Here we asked if the transplantation of normal human glial progenitor cells (hGPCs) into adult HD mice might similarly ameliorate phenotype. We found that the introduction of hGPCs into the striata of adult R6/2 HD mice significantly ameliorated their motor and cognitive phenotypes, extended their survival, and rescued aspects of medium spiny neuronal dendritic architecture. To establish the basis for this effect, we used retrograde labeling of striatal MSNs with glycoprotein-deleted rabies virus in hGPC-engrafted adult R6/2 mice to discover that the dendritic architecture of striatal MSNs was partially restored in adult-engrafted mice. These findings suggest that glial replacement may delay disease progression in HD, and that this is associated with the dynamic reorganization of medium spiny neuron dendritic architecture.
Published in
Human glial progenitors transplanted into Huntington disease mice normalize neuronal gene expression, dendritic structure, and behavior
Villanueva CB, Huynh NPT, Mariani JN et al. · Cell reports 2025 · PMID 40503942 · doi:10.1016/j.celrep.2025.115762
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Also filed as BioProject PRJNA873097 and SRA study SRP394345. Searching any of these in the dataset finder brings you back here.

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